dbSNP rs28362679: BTNL2:p.Ser334Leu (chr6-32396116-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001304561.2(BTNL2):c.1001C>T(p.Ser334Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,056 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.018 ( 41 hom., cov: 32)

Exomes 𝑓: 0.014 ( 328 hom. )

Consequence

BTNL2
NM_001304561.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29

Publications

19 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=0.012574613).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0184 (2805/152272) while in subpopulation EAS AF = 0.0238 (123/5174). AF 95% confidence interval is 0.0204. There are 41 homozygotes in GnomAd4. There are 1313 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.1001C>T	p.Ser334Leu	missense_variant	Exon 5 of 8	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-9338G>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.1001C>T	p.Ser334Leu	missense_variant	Exon 5 of 8	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2793

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.0239

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0186

GnomAD2 exomes

AF:

0.0177

AC:

4361

AN:

246622

AF XY:

0.0183

show subpopulations

Gnomad AFR exome

AF:

0.0210

Gnomad AMR exome

AF:

0.00951

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.0263

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0206

Gnomad OTH exome

AF:

0.0174

GnomAD4 exome

AF:

0.0136

AC:

19812

AN:

1460784

Hom.:

328

Cov.:

AF XY:

0.0144

AC XY:

10491

AN XY:

726710

show subpopulations

African (AFR)

AF:

0.0194

AC:

648

AN:

33476

American (AMR)

AF:

0.0109

AC:

487

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0177

AC:

462

AN:

26136

East Asian (EAS)

AF:

0.0153

AC:

608

AN:

39700

South Asian (SAS)

AF:

0.0147

AC:

1265

AN:

86256

European-Finnish (FIN)

AF:

0.0104

AC:

542

AN:

52330

Middle Eastern (MID)

AF:

0.0430

AC:

248

AN:

5768

European-Non Finnish (NFE)

AF:

0.0132

AC:

14646

AN:

1112010

Other (OTH)

AF:

0.0150

AC:

906

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1128

2256

3383

4511

5639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.0184

AC:

2805

AN:

152272

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1313

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0206

AC:

855

AN:

41546

American (AMR)

AF:

0.0159

AC:

243

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3470

East Asian (EAS)

AF:

0.0238

AC:

123

AN:

5174

South Asian (SAS)

AF:

0.0141

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0130

AC:

138

AN:

10602

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0182

AC:

1238

AN:

68030

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

132

264

396

528

660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0199

Hom.:

168

Bravo

AF:

0.0187

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.0199

AC:

ESP6500EA

AF:

0.0185

AC:

100

ExAC

AF:

0.0181

AC:

2152

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0293

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

T;T;.

Eigen

Benign

0.078

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.66

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;M;.

PhyloP100

2.3

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.6

.;D;D

REVEL

Benign

0.078

Sift

Benign

0.048

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.25

.;B;.

Vest4

0.14

MPC

0.48

ClinPred

0.020

GERP RS

5.2

Varity_R

0.24

gMVP

0.62

Mutation Taster

=97/3

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