rs41281027

Variant names:

• chr9-101368187-C-G
• rs41281027
• NM_001701.4:c.602G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-101368187-C-G
• chr9-101368187-C-T

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.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. 15/21 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. 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:5
• Conservation: PhyloP100: -1.25
• Publications: 16 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Laboratory for Molecular Medicine
• 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=0.0026787817).
• BP6: Variant 9-101368187-C-G is Benign according to our data. Variant chr9-101368187-C-G is described in ClinVar as Benign. ClinVar VariationId is 258173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
BAAT	NM_001701.4	c.602G>C	p.Arg201Pro	missense_variant	Exon 3 of 4	ENST00000259407.7	NP_001692.1
BAAT	NM_001127610.2	c.602G>C	p.Arg201Pro	missense_variant	Exon 3 of 4		NP_001121082.1
BAAT	NM_001374715.1	c.602G>C	p.Arg201Pro	missense_variant	Exon 3 of 4		NP_001361644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAAT	ENST00000259407.7	c.602G>C	p.Arg201Pro	missense_variant	Exon 3 of 4	1	NM_001701.4	ENSP00000259407.2

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

GnomAD2 exomes AF: 0.139 AC: 35061 AN: 251358 AF XY: 0.143

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 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

African (AFR) AF: 0.219 AC: 7135 AN: 32562

American (AMR) AF: 0.135 AC: 5942 AN: 43914

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3062 AN: 24524

East Asian (EAS) AF: 0.0794 AC: 2895 AN: 36440

South Asian (SAS) AF: 0.188 AC: 16137 AN: 86052

European-Finnish (FIN) AF: 0.104 AC: 5254 AN: 50552

Middle Eastern (MID) AF: 0.199 AC: 1105 AN: 5558

European-Non Finnish (NFE) AF: 0.156 AC: 170533 AN: 1095400

Other (OTH) AF: 0.153 AC: 8927 AN: 58188

GnomAD4 genome AF: 0.158 AC: 23836 AN: 151122 Hom.: 2058 Cov.: 32 AF XY: 0.155 AC XY: 11430 AN XY: 73874

African (AFR) AF: 0.212 AC: 8754 AN: 41302

American (AMR) AF: 0.145 AC: 2201 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3470

East Asian (EAS) AF: 0.0501 AC: 246 AN: 4912

South Asian (SAS) AF: 0.192 AC: 884 AN: 4614

European-Finnish (FIN) AF: 0.0905 AC: 956 AN: 10566

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9934 AN: 67802

Other (OTH) AF: 0.148 AC: 311 AN: 2104

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypercholanemia, familial 1 Benign:1

Jan 13, 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. -

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
PhyloP100		-1.3
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
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: rs41281027; hg19: chr9-104130469;