chr9-101360542-A-G

Position:

• chr9-101360542-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001701.4(BAAT):​c.*1886T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,266 control chromosomes in the GnomAD database, including 2,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2886 hom., cov: 32)
  • Exomes 𝑓: 0.18 (3 hom.)
• Consequence: BAAT NM_001701.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.231

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-101360542-A-G is Benign according to our data. Variant chr9-101360542-A-G is described in ClinVar as [Benign]. Clinvar id is 364248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAAT	NM_001701.4	c.*1886T>C		3_prime_UTR_variant	4/4	ENST00000259407.7
BAAT	NM_001127610.2	c.*1886T>C		3_prime_UTR_variant	4/4
BAAT	NM_001374715.1	c.*1886T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAAT	ENST00000259407.7	c.*1886T>C		3_prime_UTR_variant	4/4	1	NM_001701.4	P1
	ENST00000447628.2	n.1127+180A>G		intron_variant, non_coding_transcript_variant
BAAT	ENST00000674791.1	c.762+2381T>C		intron_variant, NMD_transcript_variant
BAAT	ENST00000674909.1	c.804+2339T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27229 AN: 151992 Hom.: 2876 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.179 AC: 28 AN: 156 Hom.: 3 Cov.: 0 AF XY: 0.178 AC XY: 21 AN XY: 118

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.179 AC: 27274 AN: 152110 Hom.: 2886 Cov.: 32 AF XY: 0.176 AC XY: 13102 AN XY: 74368

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0472

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0901

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.162

Alfa AF: 0.0769 Hom.: 138

Bravo AF: 0.186

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs10123392; hg19: chr9-104122824;