rs13195509

chr6-26463432-G-A

Variant summary

Our verdict is Benign. Variant got -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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BTN2A1	NM_007049.5	c.619G>A	p.Val207Met	missense_variant	4/8	ENST00000312541.10
BTN2A1	NM_001197233.3	c.436G>A	p.Val146Met	missense_variant	3/7
BTN2A1	NM_078476.4	c.619G>A	p.Val207Met	missense_variant	4/8
BTN2A1	NM_001197234.3	c.619G>A	p.Val207Met	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN2A1	ENST00000312541.10	c.619G>A	p.Val207Met	missense_variant	4/8	1	NM_007049.5	P1
	ENST00000707189.1	n.1000-89755G>A		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-69273G>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.0568 AC: 14278 AN: 251410 Hom.: 612 AF XY: 0.0575 AC XY: 7811 AN XY: 135870

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 SAS exome AF: 0.0281

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

Gnomad4 AFR exome AF: 0.0422

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.0208

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.0288

Gnomad4 FIN exome AF: 0.0500

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.0765

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

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.00618

Gnomad4 SAS AF: 0.0233

Gnomad4 FIN AF: 0.0452

Gnomad4 NFE AF: 0.0941

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0806 Hom.: 1469

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
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
MutationTaster	Benign	1.0	P;P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs13195509; hg19: chr6-26463660;