Variant rs28362677 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.1140G>A(p.Met380Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,610,748 control chromosomes in the GnomAD database, including 20,129 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 1810 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18319 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00500

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=0.026081413).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.1140G>A	p.Met380Ile	missense_variant	6/8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-10490C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.1140G>A	p.Met380Ile	missense_variant	6/8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22975

AN:

151978

Hom.:

1810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0791

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.153

AC:

38301

AN:

249680

Hom.:

3248

AF XY:

0.154

AC XY:

20824

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0789

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.153

AC:

223731

AN:

1458652

Hom.:

18319

Cov.:

AF XY:

0.154

AC XY:

111479

AN XY:

725472

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.0806

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.151

AC:

22975

AN:

152096

Hom.:

1810

Cov.:

AF XY:

0.157

AC XY:

11643

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.0791

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.141

Hom.:

2373

Bravo

AF:

0.137

TwinsUK

AF:

0.121

AC:

448

ALSPAC

AF:

0.128

AC:

494

ESP6500AA

AF:

0.125

AC:

551

ESP6500EA

AF:

0.144

AC:

1241

ExAC

AF:

0.154

AC:

18762

Asia WGS

AF:

0.155

AC:

538

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.5

DANN

Benign

0.65

DEOGEN2

Benign

0.0020

T;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.047

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

0.14

.;N;N

REVEL

Benign

0.095

Sift

Benign

0.22

.;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.047

MutPred

0.13

Loss of disorder (P = 0.0591);Loss of disorder (P = 0.0591);.;

MPC

0.40

ClinPred

0.0096

GERP RS

3.3

Varity_R

0.27

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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