9-101362382-C-T

Variant names:

• chr9-101362382-C-T
• rs2229594
• NM_001701.4:c.*46G>A

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.*46G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,581,680 control chromosomes in the GnomAD database, including 524,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46941 hom., cov: 31)
  • Exomes 𝑓: 0.82 (477598 hom.)
• Consequence: BAAT NM_001701.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.284

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 (BayesDel_noAF=-0.88).
• BP6: Variant 9-101362382-C-T is Benign according to our data. Variant chr9-101362382-C-T is described in ClinVar as [Benign]. Clinvar id is 364275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAAT	NM_001701.4	c.*46G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000259407.7	NP_001692.1
BAAT	NM_001127610.2	c.*46G>A		3_prime_UTR_variant	Exon 4 of 4		NP_001121082.1
BAAT	NM_001374715.1	c.*46G>A		3_prime_UTR_variant	Exon 4 of 4		NP_001361644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAAT	ENST00000259407	c.*46G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_001701.4	ENSP00000259407.2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118953 AN: 151916 Hom.: 46910 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.847

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.810

GnomAD3 exomes AF: 0.784 AC: 188491 AN: 240452 Hom.: 74460 AF XY: 0.785 AC XY: 102103 AN XY: 130098

Gnomad AFR exome AF: 0.708

Gnomad AMR exome AF: 0.724

Gnomad ASJ exome AF: 0.823

Gnomad EAS exome AF: 0.653

Gnomad SAS exome AF: 0.698

Gnomad FIN exome AF: 0.859

Gnomad NFE exome AF: 0.839

Gnomad OTH exome AF: 0.812

GnomAD4 exome AF: 0.815 AC: 1165837 AN: 1429646 Hom.: 477598 Cov.: 27 AF XY: 0.813 AC XY: 579523 AN XY: 712470

Gnomad4 AFR exome AF: 0.703

Gnomad4 AMR exome AF: 0.731

Gnomad4 ASJ exome AF: 0.818

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.701

Gnomad4 FIN exome AF: 0.856

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.804

GnomAD4 genome AF: 0.783 AC: 119023 AN: 152034 Hom.: 46941 Cov.: 31 AF XY: 0.781 AC XY: 58018 AN XY: 74306

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.802

Alfa AF: 0.824 Hom.: 74013

Bravo AF: 0.774

Asia WGS AF: 0.666 AC: 2315 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypercholanemia, familial 1 Benign:2

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. -

Jul 14, 2021

Genome-Nilou Lab

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

- -

Nov 10, 2018

GeneDx

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
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.71

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: rs2229594; hg19: chr9-104124664; COSMIC: COSV52291743; COSMIC: COSV52291743;