dbSNP rs28362680: BTNL2:p.Ala202Val (chr6-32403039-G-A) – 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.605C>T(p.Ala202Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 1,612,502 control chromosomes in the GnomAD database, including 11,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 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 0.12 ( 1345 hom., cov: 32)

Exomes 𝑓: 0.096 ( 9776 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

37 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=0.0053502023).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.605C>T	p.Ala202Val	missense_variant	Exon 3 of 8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1 link	n.303-2415G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.605C>T	p.Ala202Val	missense_variant	Exon 3 of 8	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18497

AN:

151930

Hom.:

1342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0817

Gnomad OTH

AF:

0.134

GnomAD2 exomes

AF:

0.139

AC:

34330

AN:

246410

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.0850

Gnomad EAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.0832

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.0957

AC:

139714

AN:

1460454

Hom.:

9776

Cov.:

AF XY:

0.0979

AC XY:

71145

AN XY:

726540

show subpopulations

African (AFR)

AF:

0.142

AC:

4758

AN:

33468

American (AMR)

AF:

0.204

AC:

9104

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0845

AC:

2207

AN:

26130

East Asian (EAS)

AF:

0.351

AC:

13945

AN:

39694

South Asian (SAS)

AF:

0.169

AC:

14536

AN:

86242

European-Finnish (FIN)

AF:

0.170

AC:

8867

AN:

52292

Middle Eastern (MID)

AF:

0.0990

AC:

571

AN:

5768

European-Non Finnish (NFE)

AF:

0.0713

AC:

79228

AN:

1111790

Other (OTH)

AF:

0.108

AC:

6498

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.424

Heterozygous variant carriers

7171

14341

21512

28682

35853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3060

6120

9180

12240

15300

<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:

0.122

AC:

18510

AN:

152048

Hom.:

1345

Cov.:

AF XY:

0.128

AC XY:

9500

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.140

AC:

5799

AN:

41462

American (AMR)

AF:

0.143

AC:

2185

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

271

AN:

3470

East Asian (EAS)

AF:

0.305

AC:

1570

AN:

5150

South Asian (SAS)

AF:

0.193

AC:

931

AN:

4814

European-Finnish (FIN)

AF:

0.176

AC:

1861

AN:

10562

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0816

AC:

5550

AN:

68000

Other (OTH)

AF:

0.133

AC:

281

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

776

1553

2329

3106

3882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.0988

Hom.:

2193

Bravo

AF:

0.118

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0685

AC:

264

ESP6500AA

AF:

0.132

AC:

398

ESP6500EA

AF:

0.0879

AC:

476

ExAC

AF:

0.137

AC:

16186

Asia WGS

AF:

0.221

AC:

768

AN:

3478

EpiCase

AF:

0.0781

EpiControl

AF:

0.0758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.4

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0022

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0055

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-3.1

.;N

PhyloP100

1.4

PrimateAI

Benign

0.41

PROVEAN

Benign

3.0

.;N

REVEL

Benign

0.14

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.027

MPC

0.36

ClinPred

0.0049

GERP RS

4.4

Varity_R

0.029

gMVP

0.096

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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