9-101368187-C-G

Variant names:

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

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: 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=0.0026787817).
• 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.

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.602G>C	p.Arg201Pro	missense	Exon 3 of 4	NP_001692.1	Q14032
	BAAT	NM_001127610.2		c.602G>C	p.Arg201Pro	missense	Exon 3 of 4	NP_001121082.1	Q14032
	BAAT	NM_001374715.1		c.602G>C	p.Arg201Pro	missense	Exon 3 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.602G>C	p.Arg201Pro	missense	Exon 3 of 4	ENSP00000259407.2	Q14032
	BAAT	ENST00000395051.4	TSL:1	c.602G>C	p.Arg201Pro	missense	Exon 3 of 4	ENSP00000378491.3	Q14032
	BAAT	ENST00000674556.1		c.602G>C	p.Arg201Pro	missense	Exon 3 of 4	ENSP00000501610.1	Q14032

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hypercholanemia, familial 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.020	N
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.67	N
PhyloP100		-1.3
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.031
Sift	Benign	0.090	T
Sift4G	Benign	0.16	T
Polyphen		0.0	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;