rs41281027

chr9-101368187-C-Gchr9-101368187-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001701.4(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. 13/19 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. R201H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.16 (2058 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17428 hom.)
• Consequence: BAAT NM_001701.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.25

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]

ACMG classification

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	UniProt
BAAT	NM_001701.4	c.602G>C	p.Arg201Pro	missense_variant	3/4	ENST00000259407.7
BAAT	NM_001127610.2	c.602G>C	p.Arg201Pro	missense_variant	3/4
BAAT	NM_001374715.1	c.602G>C	p.Arg201Pro	missense_variant	3/4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23803 AN: 150986 Hom.: 2052 Cov.: 32

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

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.: 33 AF XY: 0.155 AC XY: 110761 AN XY: 713670

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.: 32 AF XY: 0.155 AC XY: 11430 AN XY: 73874

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

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	T
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	N
MetaRNN	Benign	0.0027	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.67	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.19	T
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	T
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

Other links and lift over

dbSNP: rs41281027; hg19: chr9-104130469;