Variant rs34423804 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.848A>T(p.Asp283Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,612,962 control chromosomes in the GnomAD database, including 1,141 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.017 ( 77 hom., cov: 32)

Exomes 𝑓: 0.016 ( 1064 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.880

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:

BTNL2 (HGNC:):

BTNL2 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=0.0021602213).

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 linkuse as main transcript	c.848A>T	p.Asp283Val	missense_variant	5/8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 linkuse as main transcript	n.303-9185T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 linkuse as main transcript	c.848A>T	p.Asp283Val	missense_variant	5/8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2658

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00572

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0246

AC:

6051

AN:

246452

Hom.:

183

AF XY:

0.0271

AC XY:

3642

AN XY:

134334

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0496

Gnomad EAS exome

AF:

0.0822

Gnomad SAS exome

AF:

0.0811

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00691

Gnomad OTH exome

AF:

0.0231

GnomAD4 exome

AF:

0.0160

AC:

23318

AN:

1460710

Hom.:

1064

Cov.:

AF XY:

0.0183

AC XY:

13320

AN XY:

726676

show subpopulations

Gnomad4 AFR exome

AF:

0.0189

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.0489

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.0828

Gnomad4 FIN exome

AF:

0.000268

Gnomad4 NFE exome

AF:

0.00525

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.0175

AC:

2661

AN:

152252

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1420

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0206

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00572

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.0160

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.0192

AC:

ESP6500EA

AF:

0.00886

AC:

ExAC

AF:

0.0254

AC:

3017

Asia WGS

AF:

0.0820

AC:

283

AN:

3478

EpiCase

AF:

0.00802

EpiControl

AF:

0.00699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0053

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.0094

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.0

.;N;.

PrimateAI

Benign

0.46

PROVEAN

Benign

0.65

.;N;N

REVEL

Benign

0.053

Sift

Benign

0.47

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.028

MPC

0.52

ClinPred

0.0018

GERP RS

4.0

Varity_R

0.078

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 6

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