Variant rs2076530 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.1078A>G(p.Ser360Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,605,698 control chromosomes in the GnomAD database, including 154,229 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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 0.40 ( 12372 hom., cov: 32)

Exomes 𝑓: 0.44 ( 141857 hom. )

Consequence

BTNL2
NM_001304561.2 missense, splice_region

Scores

Splicing: ADA: 0.00002158

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

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=0.0020704567).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 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.1078A>G	p.Ser360Gly	missense_variant, splice_region_variant	5/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1 linkuse as main transcript	n.303-9415T>C		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.1078A>G	p.Ser360Gly	missense_variant, splice_region_variant	5/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1 linkuse as main transcript	n.627+5286T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61050

AN:

152002

Hom.:

12370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.400

GnomAD3 exomes

AF:

0.423

AC:

103271

AN:

244188

Hom.:

22391

AF XY:

0.422

AC XY:

56164

AN XY:

133068

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.497

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.399

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.439

AC:

638248

AN:

1453578

Hom.:

141857

Cov.:

AF XY:

0.437

AC XY:

315523

AN XY:

722736

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.493

Gnomad4 ASJ exome

AF:

0.408

Gnomad4 EAS exome

AF:

0.408

Gnomad4 SAS exome

AF:

0.402

Gnomad4 FIN exome

AF:

0.457

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

AF:

0.401

AC:

61070

AN:

152120

Hom.:

12372

Cov.:

AF XY:

0.403

AC XY:

29967

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.442

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.394

Alfa

AF:

0.416

Hom.:

22359

Bravo

AF:

0.402

TwinsUK

AF:

0.447

AC:

1657

ALSPAC

AF:

0.471

AC:

1814

ESP6500AA

AF:

0.323

AC:

974

ESP6500EA

AF:

0.438

AC:

2375

ExAC

AF:

0.418

AC:

48947

Asia WGS

AF:

0.330

AC:

1149

AN:

3478

EpiCase

AF:

0.420

EpiControl

AF:

0.420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

Cadd

Benign

Dann

Benign

0.60

DEOGEN2

Benign

0.0029

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.0046

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.99

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

PrimateAI

Benign

0.37

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.039

MPC

0.33

ClinPred

0.0014

GERP RS

3.4

Varity_R

0.053

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.044

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