Variant 6-26463346-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007049.5(BTN2A1):c.533G>T(p.Trp178Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0787 in 1,613,746 control chromosomes in the GnomAD database, including 6,473 homozygotes. In-silico tool predicts 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W178C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.051 ( 271 hom., cov: 31)

Exomes 𝑓: 0.082 ( 6202 hom. )

Consequence

BTN2A1
NM_007049.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.21

Variant links:

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]

BTN2A1 links:

ENSG00000291336 (HGNC:):

ENSG00000291336 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004269719).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN2A1	NM_007049.5 linkuse as main transcript	c.533G>T	p.Trp178Leu	missense_variant	4/8	ENST00000312541.10	NP_008980.1	Q7KYR7-2
BTN2A1	NM_001197233.3 linkuse as main transcript	c.350G>T	p.Trp117Leu	missense_variant	3/7		NP_001184162.1	Q7KYR7-5
BTN2A1	NM_078476.4 linkuse as main transcript	c.533G>T	p.Trp178Leu	missense_variant	4/8		NP_510961.1	Q7KYR7-4
BTN2A1	NM_001197234.3 linkuse as main transcript	c.533G>T	p.Trp178Leu	missense_variant	4/8		NP_001184163.1	Q7KYR7-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN2A1	ENST00000312541.10 linkuse as main transcript	c.533G>T	p.Trp178Leu	missense_variant	4/8	1	NM_007049.5	ENSP00000312158.5		Q7KYR7-2

Frequencies

GnomAD3 genomes

AF:

0.0515

AC:

7820

AN:

151970

Hom.:

271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0291

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0249

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0821

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0452

AC:

11355

AN:

251344

Hom.:

445

AF XY:

0.0448

AC XY:

6083

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.0788

Gnomad OTH exome

AF:

0.0419

GnomAD4 exome

AF:

0.0816

AC:

119215

AN:

1461658

Hom.:

6202

Cov.:

AF XY:

0.0783

AC XY:

56899

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.0283

Gnomad4 AMR exome

AF:

0.0176

Gnomad4 ASJ exome

AF:

0.0200

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0400

Gnomad4 NFE exome

AF:

0.0997

Gnomad4 OTH exome

AF:

0.0655

GnomAD4 genome

AF:

0.0514

AC:

7818

AN:

152088

Hom.:

271

Cov.:

AF XY:

0.0467

AC XY:

3475

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0290

Gnomad4 AMR

AF:

0.0249

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0388

Gnomad4 NFE

AF:

0.0820

Gnomad4 OTH

AF:

0.0351

Alfa

AF:

0.0622

Hom.:

227

Bravo

AF:

0.0500

TwinsUK

AF:

0.119

AC:

442

ALSPAC

AF:

0.106

AC:

410

ESP6500AA

AF:

0.0311

AC:

137

ESP6500EA

AF:

0.0801

AC:

689

ExAC

AF:

0.0463

AC:

5619

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

.;T;.;.

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.096

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

D;D;D;D

MetaRNN

Benign

0.0043

T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Pathogenic

4.1

.;H;H;H

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-11

D;D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;.;.

Vest4

0.36

MPC

0.54

ClinPred

0.12

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.81

gMVP

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over