Genetic Variant BTNL2:p.Met295Val (chr6-32396234-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001304561.2(BTNL2):c.883A>G(p.Met295Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,612,956 control chromosomes in the GnomAD database, including 1,125 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 68 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1057 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

20 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016432703).

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 rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.883A>G	p.Met295Val	missense_variant	Exon 5 of 8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-9220T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.883A>G	p.Met295Val	missense_variant	Exon 5 of 8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1859

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.0453

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00551

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0232

AC:

5722

AN:

246684

AF XY:

0.0262

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00946

Gnomad ASJ exome

AF:

0.0498

Gnomad EAS exome

AF:

0.0823

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00684

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0154

AC:

22510

AN:

1460696

Hom.:

1057

Cov.:

AF XY:

0.0179

AC XY:

12974

AN XY:

726682

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

33480

American (AMR)

AF:

0.00993

AC:

444

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0489

AC:

1278

AN:

26134

East Asian (EAS)

AF:

0.161

AC:

6407

AN:

39686

South Asian (SAS)

AF:

0.0828

AC:

7137

AN:

86240

European-Finnish (FIN)

AF:

0.000267

AC:

AN:

52344

Middle Eastern (MID)

AF:

0.0383

AC:

221

AN:

5768

European-Non Finnish (NFE)

AF:

0.00521

AC:

5790

AN:

1111948

Other (OTH)

AF:

0.0194

AC:

1170

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

1226

2453

3679

4906

6132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

334

668

1002

1336

1670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0122

AC:

1857

AN:

152260

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1054

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41560

American (AMR)

AF:

0.00928

AC:

142

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0453

AC:

157

AN:

3464

East Asian (EAS)

AF:

0.109

AC:

563

AN:

5170

South Asian (SAS)

AF:

0.100

AC:

484

AN:

4822

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00551

AC:

375

AN:

68016

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00989

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00132

AC:

ESP6500EA

AF:

0.00886

AC:

ExAC

AF:

0.0237

AC:

2815

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

EpiCase

AF:

0.00796

EpiControl

AF:

0.00700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.069

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.015

T;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.020

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.

PhyloP100

-1.1

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.24

.;N;N

REVEL

Benign

0.043

Sift

Benign

0.14

.;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.022

MPC

0.37

ClinPred

0.011

GERP RS

-10

Varity_R

0.10

gMVP

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over