rs61755096

Variant names:

• chr9-101362774-A-G
• rs61755096
• NM_001701.4:c.911T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-101362774-A-G
• chr9-101362774-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 15/21 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -7.05
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• hypercholanemia, familial 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• bile acid CoA:amino acid N-acyltransferase deficiency

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• familial hypercholanemia

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Laboratory for Molecular Medicine, Orphanet
• bile acid conjugation defect 1

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 258174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001701.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAAT	NM_001701.4	MANE Select	c.911T>C	p.Val304Ala	missense	Exon 4 of 4	NP_001692.1	Q14032
	BAAT	NM_001127610.2		c.911T>C	p.Val304Ala	missense	Exon 4 of 4	NP_001121082.1	Q14032
	BAAT	NM_001374715.1		c.911T>C	p.Val304Ala	missense	Exon 4 of 4	NP_001361644.1	Q14032

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAAT	ENST00000259407.7	TSL:1 MANE Select	c.911T>C	p.Val304Ala	missense	Exon 4 of 4	ENSP00000259407.2	Q14032
	BAAT	ENST00000395051.4	TSL:1	c.911T>C	p.Val304Ala	missense	Exon 4 of 4	ENSP00000378491.3	Q14032
	BAAT	ENST00000674556.1		c.911T>C	p.Val304Ala	missense	Exon 4 of 4	ENSP00000501610.1	Q14032

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2931 AN: 152190 Hom.: 48 Cov.: 32

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

GnomAD2 exomes AF: 0.0254 AC: 6368 AN: 251134 AF XY: 0.0275

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 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.: 33 AF XY: 0.0286 AC XY: 20833 AN XY: 727230

African (AFR) AF: 0.00385 AC: 129 AN: 33480

American (AMR) AF: 0.0187 AC: 835 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 1824 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.0432 AC: 3725 AN: 86258

European-Finnish (FIN) AF: 0.00279 AC: 149 AN: 53420

Middle Eastern (MID) AF: 0.0461 AC: 266 AN: 5768

European-Non Finnish (NFE) AF: 0.0287 AC: 31900 AN: 1111994

Other (OTH) AF: 0.0281 AC: 1695 AN: 60396

GnomAD4 genome AF: 0.0192 AC: 2928 AN: 152308 Hom.: 48 Cov.: 32 AF XY: 0.0185 AC XY: 1375 AN XY: 74472

African (AFR) AF: 0.00459 AC: 191 AN: 41582

American (AMR) AF: 0.0232 AC: 355 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 230 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4826

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0275 AC: 1868 AN: 68020

Other (OTH) AF: 0.0326 AC: 69 AN: 2116

Alfa AF: 0.0282 Hom.: 274

Bravo AF: 0.0207

TwinsUK AF: 0.0235 AC: 87

ALSPAC AF: 0.0272 AC: 105

ESP6500AA AF: 0.00590 AC: 26

ESP6500EA AF: 0.0319 AC: 274

ExAC AF: 0.0253 AC: 3065

Asia WGS AF: 0.0120 AC: 42 AN: 3478

EpiCase AF: 0.0338

EpiControl AF: 0.0333

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Hypercholanemia, familial 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0010
DANN	Benign	0.32
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.028	N
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N
PhyloP100		-7.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.041
Sift	Benign	0.60	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.034
MPC		0.051
ClinPred		0.0056	T
GERP RS		-9.9
Varity_R		0.022
gMVP		0.14
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61755096; hg19: chr9-104125056; COSMIC: COSV52290245; COSMIC: COSV52290245;