9-101362774-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001701.4(BAAT):c.911T>C(p.Val304Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,614,172 control chromosomes in the GnomAD database, including 793 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 48 hom., cov: 32)

Exomes 𝑓: 0.028 ( 745 hom. )

Consequence

BAAT
NM_001701.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -7.05

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=0.0020793974).

BP6

Variant 9-101362774-A-G is Benign according to our data. Variant chr9-101362774-A-G is described in ClinVar as [Benign]. Clinvar id is 258174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-101362774-A-G is described in Lovd as [Benign]. Variant chr9-101362774-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0192 (2928/152308) while in subpopulation SAS AF= 0.0354 (171/4826). AF 95% confidence interval is 0.0311. There are 48 homozygotes in gnomad4. There are 1375 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAAT	NM_001701.4 link	c.911T>C	p.Val304Ala	missense_variant	Exon 4 of 4	ENST00000259407.7	NP_001692.1	Q14032
BAAT	NM_001127610.2 link	c.911T>C	p.Val304Ala	missense_variant	Exon 4 of 4		NP_001121082.1	Q14032
BAAT	NM_001374715.1 link	c.911T>C	p.Val304Ala	missense_variant	Exon 4 of 4		NP_001361644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAAT	ENST00000259407.7 link	c.911T>C	p.Val304Ala	missense_variant	Exon 4 of 4	1	NM_001701.4	ENSP00000259407.2		Q14032

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2931

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00461

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.0662

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0275

Gnomad OTH

AF:

0.0334

GnomAD3 exomes

AF:

0.0254

AC:

6368

AN:

251134

Hom.:

129

AF XY:

0.0275

AC XY:

3733

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0710

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0439

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.0302

Gnomad OTH exome

AF:

0.0284

GnomAD4 exome

AF:

0.0277

AC:

40526

AN:

1461864

Hom.:

745

Cov.:

AF XY:

0.0286

AC XY:

20833

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00385

Gnomad4 AMR exome

AF:

0.0187

Gnomad4 ASJ exome

AF:

0.0698

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0432

Gnomad4 FIN exome

AF:

0.00279

Gnomad4 NFE exome

AF:

0.0287

Gnomad4 OTH exome

AF:

0.0281

GnomAD4 genome

AF:

0.0192

AC:

2928

AN:

152308

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1375

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00459

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.0662

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0354

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.0275

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0306

Hom.:

145

Bravo

AF:

0.0207

TwinsUK

AF:

0.0235

AC:

ALSPAC

AF:

0.0272

AC:

105

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0319

AC:

274

ExAC

AF:

0.0253

AC:

3065

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0338

EpiControl

AF:

0.0333

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypercholanemia, familial 1

Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0010

DANN

Benign

0.32

DEOGEN2

Benign

0.0077

T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.028

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.55

N;N

REVEL

Benign

0.041

Sift

Benign

0.60

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0

B;B

Vest4

0.034

MPC

0.051

ClinPred

0.0056

GERP RS

-9.9

Varity_R

0.022

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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