9-101371346-C-T

Position:

chr9-101371346-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 257518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-101371346-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
BAAT	NM_001701.4 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/4	ENST00000259407.7	NP_001692.1	Q14032
BAAT	NM_001127610.2 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/4		NP_001121082.1	Q14032
BAAT	NM_001374715.1 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/4		NP_001361644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAAT	ENST00000259407.7 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/4	1	NM_001701.4	ENSP00000259407.2		Q14032

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

GnomAD3 exomes

AF:

0.647

AC:

162237

AN:

250776

Hom.:

53442

AF XY:

0.644

AC XY:

87332

AN XY:

135540

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 SAS exome

AF:

0.508

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

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.601

Gnomad4 ASJ exome

AF:

0.699

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.513

Gnomad4 FIN exome

AF:

0.759

Gnomad4 NFE exome

AF:

0.689

Gnomad4 OTH exome

AF:

0.659

GnomAD4 genome

AF:

0.630

AC:

95676

AN:

151976

Hom.:

30779

Cov.:

AF XY:

0.630

AC XY:

46759

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.497

Gnomad4 AMR

AF:

0.622

Gnomad4 ASJ

AF:

0.711

Gnomad4 EAS

AF:

0.606

Gnomad4 SAS

AF:

0.497

Gnomad4 FIN

AF:

0.763

Gnomad4 NFE

AF:

0.696

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.684

Hom.:

72236

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 15, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Hypercholanemia, familial 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Bile acid conjugation defect 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over