dbSNP rs9268480: BTNL2:p.Gln350Gln (chr6-32396067-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001304561.2(BTNL2):c.1050G>A(p.Gln350Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,612,570 control chromosomes in the GnomAD database, including 62,843 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 0.24 ( 4552 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58291 hom. )

Consequence

BTNL2
NM_001304561.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0350

Publications

72 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

Synonymous conserved (PhyloP=-0.035 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.1050G>A	p.Gln350Gln	synonymous_variant	Exon 5 of 8	ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1 link	n.303-9387C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.1050G>A	p.Gln350Gln	synonymous_variant	Exon 5 of 8	5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36297

AN:

152092

Hom.:

4553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.235

GnomAD2 exomes

AF:

0.258

AC:

63383

AN:

245970

AF XY:

0.255

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.276

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.277

AC:

405220

AN:

1460360

Hom.:

58291

Cov.:

AF XY:

0.274

AC XY:

199227

AN XY:

726496

show subpopulations

African (AFR)

AF:

0.168

AC:

5615

AN:

33476

American (AMR)

AF:

0.338

AC:

15128

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

7742

AN:

26128

East Asian (EAS)

AF:

0.132

AC:

5220

AN:

39690

South Asian (SAS)

AF:

0.216

AC:

18595

AN:

86248

European-Finnish (FIN)

AF:

0.194

AC:

10156

AN:

52302

Middle Eastern (MID)

AF:

0.226

AC:

1305

AN:

5766

European-Non Finnish (NFE)

AF:

0.293

AC:

325438

AN:

1111652

Other (OTH)

AF:

0.265

AC:

16021

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

14746

29492

44238

58984

73730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10974

21948

32922

43896

54870

<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:

0.239

AC:

36310

AN:

152210

Hom.:

4552

Cov.:

AF XY:

0.235

AC XY:

17463

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.180

AC:

7459

AN:

41528

American (AMR)

AF:

0.294

AC:

4496

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1057

AN:

3472

East Asian (EAS)

AF:

0.148

AC:

770

AN:

5186

South Asian (SAS)

AF:

0.231

AC:

1113

AN:

4824

European-Finnish (FIN)

AF:

0.186

AC:

1973

AN:

10598

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.275

AC:

18676

AN:

68016

Other (OTH)

AF:

0.231

AC:

488

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1428

2856

4284

5712

7140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.259

Hom.:

12063

Bravo

AF:

0.252

Asia WGS

AF:

0.163

AC:

567

AN:

3478

EpiCase

AF:

0.275

EpiControl

AF:

0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.9

(source)

DANN

Benign

0.70

PhyloP100

-0.035

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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