Variant rs28362680 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.605C>T(p.Ala202Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 1,612,502 control chromosomes in the GnomAD database, including 11,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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 0.12 ( 1345 hom., cov: 32)

Exomes 𝑓: 0.096 ( 9776 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

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:

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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=0.0053502023).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2 linkuse as main transcript	c.605C>T	p.Ala202Val	missense_variant	3/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1 linkuse as main transcript	n.303-2415G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8 linkuse as main transcript	c.605C>T	p.Ala202Val	missense_variant	3/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1 linkuse as main transcript	n.628-630G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18497

AN:

151930

Hom.:

1342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0817

Gnomad OTH

AF:

0.134

GnomAD3 exomes

AF:

0.139

AC:

34330

AN:

246410

Hom.:

3056

AF XY:

0.136

AC XY:

18281

AN XY:

134324

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.0850

Gnomad EAS exome

AF:

0.285

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.0832

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.0957

AC:

139714

AN:

1460454

Hom.:

9776

Cov.:

AF XY:

0.0979

AC XY:

71145

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.0845

Gnomad4 EAS exome

AF:

0.351

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.0713

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.122

AC:

18510

AN:

152048

Hom.:

1345

Cov.:

AF XY:

0.128

AC XY:

9500

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.0816

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.0942

Hom.:

1431

Bravo

AF:

0.118

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0685

AC:

264

ESP6500AA

AF:

0.132

AC:

398

ESP6500EA

AF:

0.0879

AC:

476

ExAC

AF:

0.137

AC:

16186

Asia WGS

AF:

0.221

AC:

768

AN:

3478

EpiCase

AF:

0.0781

EpiControl

AF:

0.0758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.4

DANN

Benign

0.70

DEOGEN2

Benign

0.0022

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0055

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Benign

0.41

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.027

MPC

0.36

ClinPred

0.0049

GERP RS

4.4

Varity_R

0.029

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

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