9-101371346-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001701.4(BAAT):c.59G>A(p.Arg20Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,613,430 control chromosomes in the GnomAD database, including 360,951 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R20K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.63 ( 30779 hom., cov: 31)

Exomes 𝑓: 0.67 ( 330172 hom. )

Consequence

BAAT
NM_001701.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.42

Publications

30 publications found

Variant links:

Genes affected

BAAT (HGNC:932): (bile acid-CoA:amino acid N-acyltransferase) The protein encoded by this gene is a liver enzyme that catalyzes the transfer of C24 bile acids from the acyl-CoA thioester to either glycine or taurine, the second step in the formation of bile acid-amino acid conjugates. The bile acid conjugates then act as a detergent in the gastrointestinal tract, which enhances lipid and fat-soluble vitamin absorption. Defects in this gene are a cause of familial hypercholanemia (FHCA). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

BAAT Gene-Disease associations (from GenCC):

hypercholanemia, familial 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
bile acid CoA:amino acid N-acyltransferase deficiency
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
familial hypercholanemia
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Laboratory for Molecular Medicine
bile acid conjugation defect 1
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

BAAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2092823E-6).

BP6

Variant 9-101371346-C-T is Benign according to our data. Variant chr9-101371346-C-T is described in ClinVar as Benign. ClinVar VariationId is 257518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
BAAT	NM_001701.4 link	c.59G>A	p.Arg20Gln	missense_variant	Exon 2 of 4	ENST00000259407.7	NP_001692.1
BAAT	NM_001127610.2 link	c.59G>A	p.Arg20Gln	missense_variant	Exon 2 of 4		NP_001121082.1
BAAT	NM_001374715.1 link	c.59G>A	p.Arg20Gln	missense_variant	Exon 2 of 4		NP_001361644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAAT	ENST00000259407.7 link	c.59G>A	p.Arg20Gln	missense_variant	Exon 2 of 4	1	NM_001701.4	ENSP00000259407.2

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95635

AN:

151856

Hom.:

30765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.745

Gnomad AMR

AF:

0.622

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.606

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.763

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.696

Gnomad OTH

AF:

0.664

GnomAD2 exomes

AF:

0.647

AC:

162237

AN:

250776

AF XY:

0.644

show subpopulations

Gnomad AFR exome

AF:

0.488

Gnomad AMR exome

AF:

0.597

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.612

Gnomad FIN exome

AF:

0.762

Gnomad NFE exome

AF:

0.700

Gnomad OTH exome

AF:

0.674

GnomAD4 exome

AF:

0.669

AC:

978399

AN:

1461454

Hom.:

330172

Cov.:

AF XY:

0.666

AC XY:

484192

AN XY:

727044

show subpopulations

African (AFR)

AF:

0.491

AC:

16445

AN:

33472

American (AMR)

AF:

0.601

AC:

26846

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

18257

AN:

26132

East Asian (EAS)

AF:

0.577

AC:

22913

AN:

39686

South Asian (SAS)

AF:

0.513

AC:

44235

AN:

86252

European-Finnish (FIN)

AF:

0.759

AC:

40354

AN:

53158

Middle Eastern (MID)

AF:

0.650

AC:

3741

AN:

5752

European-Non Finnish (NFE)

AF:

0.689

AC:

765788

AN:

1111920

Other (OTH)

AF:

0.659

AC:

39820

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

19475

38949

58424

77898

97373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19328

38656

57984

77312

96640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.630

AC:

95676

AN:

151976

Hom.:

30779

Cov.:

AF XY:

0.630

AC XY:

46759

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.497

AC:

20576

AN:

41430

American (AMR)

AF:

0.622

AC:

9497

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

2467

AN:

3468

East Asian (EAS)

AF:

0.606

AC:

3122

AN:

5156

South Asian (SAS)

AF:

0.497

AC:

2393

AN:

4818

European-Finnish (FIN)

AF:

0.763

AC:

8052

AN:

10552

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.696

AC:

47309

AN:

67962

Other (OTH)

AF:

0.658

AC:

1392

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1759

3517

5276

7034

8793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.672

Hom.:

143442

Bravo

AF:

0.618

TwinsUK

AF:

0.685

AC:

2540

ALSPAC

AF:

0.691

AC:

2665

ESP6500AA

AF:

0.506

AC:

2228

ESP6500EA

AF:

0.696

AC:

5984

ExAC

AF:

0.646

AC:

78398

Asia WGS

AF:

0.545

AC:

1896

AN:

3478

EpiCase

AF:

0.693

EpiControl

AF:

0.698

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

May 15, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypercholanemia, familial 1

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bile acid conjugation defect 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.7

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

L;L

PhyloP100

-3.4

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.10

Sift

Benign

0.43

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.048

B;B

Vest4

0.034

MPC

0.052

ClinPred

0.0051

GERP RS

-3.9

Varity_R

0.090

gMVP

0.23

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over