rs1572983

Variant names:

• chr9-101371346-C-T
• rs1572983
• NM_001701.4:c.59G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-101371346-C-T
• chr9-101371346-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001701.4(BAAT):​c.59G>A​(p.Arg20Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,613,430 control chromosomes in the GnomAD database, including 360,951 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. R20K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.63 (30779 hom., cov: 31)
  • Exomes 𝑓: 0.67 (330172 hom.)
• Consequence: BAAT NM_001701.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.42
• Publications: 30 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=1.2092823E-6).
• BP6: Variant 9-101371346-C-T is Benign according to our data. Variant chr9-101371346-C-T is described in ClinVar as Benign. ClinVar VariationId is 257518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

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.59G>A	p.Arg20Gln	missense	Exon 2 of 4	NP_001692.1	Q14032
	BAAT	NM_001127610.2		c.59G>A	p.Arg20Gln	missense	Exon 2 of 4	NP_001121082.1	Q14032
	BAAT	NM_001374715.1		c.59G>A	p.Arg20Gln	missense	Exon 2 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.59G>A	p.Arg20Gln	missense	Exon 2 of 4	ENSP00000259407.2	Q14032
	BAAT	ENST00000395051.4	TSL:1	c.59G>A	p.Arg20Gln	missense	Exon 2 of 4	ENSP00000378491.3	Q14032
	BAAT	ENST00000674556.1		c.59G>A	p.Arg20Gln	missense	Exon 2 of 4	ENSP00000501610.1	Q14032

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95635 AN: 151856 Hom.: 30765 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.664

GnomAD2 exomes AF: 0.647 AC: 162237 AN: 250776 AF XY: 0.644

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.703

Gnomad EAS exome AF: 0.612

Gnomad FIN exome AF: 0.762

Gnomad NFE exome AF: 0.700

Gnomad OTH exome AF: 0.674

GnomAD4 exome AF: 0.669 AC: 978399 AN: 1461454 Hom.: 330172 Cov.: 72 AF XY: 0.666 AC XY: 484192 AN XY: 727044

African (AFR) AF: 0.491 AC: 16445 AN: 33472

American (AMR) AF: 0.601 AC: 26846 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 18257 AN: 26132

East Asian (EAS) AF: 0.577 AC: 22913 AN: 39686

South Asian (SAS) AF: 0.513 AC: 44235 AN: 86252

European-Finnish (FIN) AF: 0.759 AC: 40354 AN: 53158

Middle Eastern (MID) AF: 0.650 AC: 3741 AN: 5752

European-Non Finnish (NFE) AF: 0.689 AC: 765788 AN: 1111920

Other (OTH) AF: 0.659 AC: 39820 AN: 60386

GnomAD4 genome AF: 0.630 AC: 95676 AN: 151976 Hom.: 30779 Cov.: 31 AF XY: 0.630 AC XY: 46759 AN XY: 74258

African (AFR) AF: 0.497 AC: 20576 AN: 41430

American (AMR) AF: 0.622 AC: 9497 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3468

East Asian (EAS) AF: 0.606 AC: 3122 AN: 5156

South Asian (SAS) AF: 0.497 AC: 2393 AN: 4818

European-Finnish (FIN) AF: 0.763 AC: 8052 AN: 10552

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47309 AN: 67962

Other (OTH) AF: 0.658 AC: 1392 AN: 2116

Alfa AF: 0.672 Hom.: 143442

Bravo AF: 0.618

TwinsUK AF: 0.685 AC: 2540

ALSPAC AF: 0.691 AC: 2665

ESP6500AA AF: 0.506 AC: 2228

ESP6500EA AF: 0.696 AC: 5984

ExAC AF: 0.646 AC: 78398

Asia WGS AF: 0.545 AC: 1896 AN: 3478

EpiCase AF: 0.693

EpiControl AF: 0.698

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Hypercholanemia, familial 1 (2)
-	-	2	not specified (2)
-	-	1	Bile acid conjugation defect 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.7
DANN	Benign	0.83
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		-3.4
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.10
Sift	Benign	0.43	T
Sift4G	Benign	0.56	T
Polyphen		0.048	B
Vest4		0.034
MPC		0.052
ClinPred		0.0051	T
GERP RS		-3.9
Varity_R		0.090
gMVP		0.23
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1572983; hg19: chr9-104133628; COSMIC: COSV52287247; COSMIC: COSV52287247;