dbSNP rs34423804: BTNL2:p.Asp283Val (chr6-32396269-T-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.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. 15/22 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 0.017 ( 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

Publications

13 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=0.0021602213).

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 rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.848A>T	p.Asp283Val	missense_variant	Exon 5 of 8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-9185T>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.848A>T	p.Asp283Val	missense_variant	Exon 5 of 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

GnomAD2 exomes

AF:

0.0246

AC:

6051

AN:

246452

AF XY:

0.0271

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 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

African (AFR)

AF:

0.0189

AC:

634

AN:

33480

American (AMR)

AF:

0.0117

AC:

521

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0489

AC:

1278

AN:

26132

East Asian (EAS)

AF:

0.162

AC:

6413

AN:

39696

South Asian (SAS)

AF:

0.0828

AC:

7143

AN:

86230

European-Finnish (FIN)

AF:

0.000268

AC:

AN:

52328

Middle Eastern (MID)

AF:

0.0394

AC:

227

AN:

5768

European-Non Finnish (NFE)

AF:

0.00525

AC:

5836

AN:

1111978

Other (OTH)

AF:

0.0207

AC:

1252

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

1284

2568

3852

5136

6420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.0175

AC:

2661

AN:

152252

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1420

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0206

AC:

856

AN:

41548

American (AMR)

AF:

0.0107

AC:

164

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

157

AN:

3470

East Asian (EAS)

AF:

0.109

AC:

562

AN:

5168

South Asian (SAS)

AF:

0.100

AC:

484

AN:

4824

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00572

AC:

389

AN:

68004

Other (OTH)

AF:

0.0180

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

137

275

412

550

687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0160

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

(source)

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;.

PhyloP100

0.88

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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