rs13195509

Variant names:

• chr6-26463432-G-A
• rs13195509
• NM_007049.5:c.619G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007049.5(BTN2A1):​c.619G>A​(p.Val207Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 1,613,960 control chromosomes in the GnomAD database, including 8,099 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (390 hom., cov: 31)
  • Exomes 𝑓: 0.094 (7709 hom.)
• Consequence: BTN2A1 NM_007049.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 55 publications found

Genes affected

BTN2A1 (HGNC:1136): (butyrophilin subfamily 2 member A1) This gene encodes a member of the immunoglobulin superfamily. The gene is located in a cluster of butyrophilin-like genes in the juxta-telomeric region of the major histocompatibility complex on chromosome 6. A pseudogene of this gene has been identified in this cluster. The encoded protein is an integral plasma membrane protein involved in lipid, fatty-acid, and sterol metabolism. Alterations in this gene may be associated with several disease states including metabolic syndrome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017808676).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN2A1	NM_007049.5	c.619G>A	p.Val207Met	missense_variant	Exon 4 of 8	ENST00000312541.10	NP_008980.1
BTN2A1	NM_001197233.3	c.436G>A	p.Val146Met	missense_variant	Exon 3 of 7		NP_001184162.1
BTN2A1	NM_078476.4	c.619G>A	p.Val207Met	missense_variant	Exon 4 of 8		NP_510961.1
BTN2A1	NM_001197234.3	c.619G>A	p.Val207Met	missense_variant	Exon 4 of 8		NP_001184163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN2A1	ENST00000312541.10	c.619G>A	p.Val207Met	missense_variant	Exon 4 of 8	1	NM_007049.5	ENSP00000312158.5

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9574 AN: 152112 Hom.: 390 Cov.: 31

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00617

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0941

Gnomad OTH AF: 0.0459

GnomAD2 exomes AF: 0.0568 AC: 14278 AN: 251410 AF XY: 0.0575

Gnomad AFR exome AF: 0.0407

Gnomad AMR exome AF: 0.0223

Gnomad ASJ exome AF: 0.0197

Gnomad EAS exome AF: 0.00560

Gnomad FIN exome AF: 0.0490

Gnomad NFE exome AF: 0.0907

Gnomad OTH exome AF: 0.0509

GnomAD4 exome AF: 0.0936 AC: 136824 AN: 1461730 Hom.: 7709 Cov.: 31 AF XY: 0.0909 AC XY: 66114 AN XY: 727152

African (AFR) AF: 0.0422 AC: 1413 AN: 33478

American (AMR) AF: 0.0228 AC: 1020 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 543 AN: 26136

East Asian (EAS) AF: 0.0220 AC: 874 AN: 39700

South Asian (SAS) AF: 0.0288 AC: 2481 AN: 86258

European-Finnish (FIN) AF: 0.0500 AC: 2672 AN: 53412

Middle Eastern (MID) AF: 0.0179 AC: 103 AN: 5768

European-Non Finnish (NFE) AF: 0.111 AC: 123098 AN: 1111878

Other (OTH) AF: 0.0765 AC: 4620 AN: 60380

GnomAD4 genome AF: 0.0629 AC: 9572 AN: 152230 Hom.: 390 Cov.: 31 AF XY: 0.0583 AC XY: 4340 AN XY: 74426

African (AFR) AF: 0.0411 AC: 1709 AN: 41552

American (AMR) AF: 0.0329 AC: 503 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.00618 AC: 32 AN: 5176

South Asian (SAS) AF: 0.0233 AC: 112 AN: 4816

European-Finnish (FIN) AF: 0.0452 AC: 480 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0941 AC: 6396 AN: 67990

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0792 Hom.: 2628

Bravo AF: 0.0610

TwinsUK AF: 0.133 AC: 495

ALSPAC AF: 0.123 AC: 473

ESP6500AA AF: 0.0427 AC: 188

ESP6500EA AF: 0.0924 AC: 795

ExAC AF: 0.0585 AC: 7098

Asia WGS AF: 0.0180 AC: 62 AN: 3478

EpiCase AF: 0.0858

EpiControl AF: 0.0821

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0051	.;T;.;.
Eigen	Benign	0.063
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.099	N
LIST_S2	Uncertain	0.87	D;D;D;D
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.7	.;M;M;M
PhyloP100		0.061
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.078	T;T;T;T
Sift4G	Benign	0.11	T;T;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.10
MPC		0.28
ClinPred		0.028	T
GERP RS		2.0
Varity_R		0.056
gMVP		0.096
Mutation Taster		=97/3	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: rs13195509; hg19: chr6-26463660; COSMIC: COSV107356290; COSMIC: COSV107356290;