rs41281027

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000259407.7(BAAT):c.602G>C(p.Arg201Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,584,312 control chromosomes in the GnomAD database, including 19,486 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R201C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.16 ( 2058 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17428 hom. )

Consequence

BAAT
ENST00000259407.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.25

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=0.0026787817).

BP6

Variant 9-101368187-C-G is Benign according to our data. Variant chr9-101368187-C-G is described in ClinVar as [Benign]. Clinvar id is 258173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-101368187-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BAAT	NM_001701.4 linkuse as main transcript	c.602G>C	p.Arg201Pro	missense_variant	3/4	ENST00000259407.7	NP_001692.1
BAAT	NM_001127610.2 linkuse as main transcript	c.602G>C	p.Arg201Pro	missense_variant	3/4		NP_001121082.1
BAAT	NM_001374715.1 linkuse as main transcript	c.602G>C	p.Arg201Pro	missense_variant	3/4		NP_001361644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAAT	ENST00000259407.7 linkuse as main transcript	c.602G>C	p.Arg201Pro	missense_variant	3/4	1	NM_001701.4	ENSP00000259407	P1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23803

AN:

150986

Hom.:

2052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.0500

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.0905

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.139

AC:

35061

AN:

251358

Hom.:

2692

AF XY:

0.143

AC XY:

19400

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.0431

Gnomad SAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.0979

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.154

AC:

220990

AN:

1433190

Hom.:

17428

Cov.:

AF XY:

0.155

AC XY:

110761

AN XY:

713670

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.0794

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.158

AC:

23836

AN:

151122

Hom.:

2058

Cov.:

AF XY:

0.155

AC XY:

11430

AN XY:

73874

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.145

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.0501

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.0905

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.132

Hom.:

1081

Bravo

AF:

0.160

TwinsUK

AF:

0.158

AC:

585

ALSPAC

AF:

0.155

AC:

596

ESP6500AA

AF:

0.217

AC:

957

ESP6500EA

AF:

0.145

AC:

1250

ExAC

AF:

0.142

AC:

17255

EpiCase

AF:

0.149

EpiControl

AF:

0.149

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hypercholanemia, familial 1

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.2

DANN

Benign

0.88

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.67

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.031

Sift

Benign

0.090

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0

B;B

Vest4

0.052

MPC

0.059

ClinPred

0.00061

GERP RS

-3.1

Varity_R

0.087

gMVP

0.55

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