Variant rs41417449 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001304561.2(BTNL2):c.883A>G(p.Met295Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,612,956 control chromosomes in the GnomAD database, including 1,125 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 68 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1057 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Variant links:

Genes affected

BTNL2 (HGNC:1142): (butyrophilin like 2) This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

BTNL2 links:

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

TSBP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016432703).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.883A>G	p.Met295Val	missense_variant	5/8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-9220T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.883A>G	p.Met295Val	missense_variant	5/8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1859

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.0453

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00551

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0232

AC:

5722

AN:

246684

Hom.:

182

AF XY:

0.0262

AC XY:

3527

AN XY:

134410

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00946

Gnomad ASJ exome

AF:

0.0498

Gnomad EAS exome

AF:

0.0823

Gnomad SAS exome

AF:

0.0817

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00684

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0154

AC:

22510

AN:

1460696

Hom.:

1057

Cov.:

AF XY:

0.0179

AC XY:

12974

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00993

Gnomad4 ASJ exome

AF:

0.0489

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.0828

Gnomad4 FIN exome

AF:

0.000267

Gnomad4 NFE exome

AF:

0.00521

Gnomad4 OTH exome

AF:

0.0194

GnomAD4 genome

AF:

0.0122

AC:

1857

AN:

152260

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1054

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.0453

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00551

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00989

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00132

AC:

ESP6500EA

AF:

0.00886

AC:

ExAC

AF:

0.0237

AC:

2815

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

EpiCase

AF:

0.00796

EpiControl

AF:

0.00700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.069

DANN

Benign

0.47

DEOGEN2

Benign

0.015

T;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.020

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.24

.;N;N

REVEL

Benign

0.043

Sift

Benign

0.14

.;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.022

MPC

0.37

ClinPred

0.011

GERP RS

-10

Varity_R

0.10

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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