Variant 6-32403082-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001304561.2(BTNL2):c.562G>A(p.Val188Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000834 in 1,612,898 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 4 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -11.2

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008282185).

BP6

Variant 6-32403082-C-T is Benign according to our data. Variant chr6-32403082-C-T is described in ClinVar as [Benign]. Clinvar id is 768075.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2 linkuse as main transcript	c.562G>A	p.Val188Met	missense_variant	3/8	ENST00000454136.8
TSBP1-AS1	NR_136245.1 linkuse as main transcript	n.303-2372C>T		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.562G>A	p.Val188Met	missense_variant	3/8	5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1 linkuse as main transcript	n.628-587C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00375

AC:

570

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00119

AC:

294

AN:

246546

Hom.:

AF XY:

0.00102

AC XY:

137

AN XY:

134398

show subpopulations

Gnomad AFR exome

AF:

0.0122

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.000602

Gnomad SAS exome

AF:

0.000527

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000190

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.000531

AC:

775

AN:

1460638

Hom.:

Cov.:

AF XY:

0.000501

AC XY:

364

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000475

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00374

AC:

570

AN:

152260

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.00445

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.000739

AC:

ExAC

AF:

0.00121

AC:

143

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.0010

DANN

Benign

0.83

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0072

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.4

.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.20

.;N

REVEL

Benign

0.27

Sift

Benign

0.14

.;T

Sift4G

Benign

0.17

T;T

Polyphen

0.93

.;P

Vest4

0.084

MVP

0.35

MPC

0.40

ClinPred

0.019

GERP RS

-8.9

Varity_R

0.014

gMVP

0.083

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over