dbSNP rs10947261: BTNL2:c.80-169C>A (chr6-32405455-G-T) – 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.80-169C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 776,078 control chromosomes in the GnomAD database, including 7,450 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 0.12 ( 1248 hom., cov: 32)

Exomes 𝑓: 0.12 ( 6202 hom. )

Consequence

BTNL2
NM_001304561.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Publications

43 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 (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.80-169C>A		intron_variant	Intron 1 of 7	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.304G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.80-169C>A		intron_variant	Intron 1 of 7	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17727

AN:

152074

Hom.:

1246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.0786

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0814

Gnomad OTH

AF:

0.131

GnomAD4 exome

AF:

0.116

AC:

72268

AN:

623886

Hom.:

6202

Cov.:

AF XY:

0.118

AC XY:

39149

AN XY:

332554

show subpopulations

African (AFR)

AF:

0.121

AC:

2053

AN:

16994

American (AMR)

AF:

0.190

AC:

6535

AN:

34390

Ashkenazi Jewish (ASJ)

AF:

0.0862

AC:

1748

AN:

20290

East Asian (EAS)

AF:

0.364

AC:

11582

AN:

31798

South Asian (SAS)

AF:

0.167

AC:

10571

AN:

63244

European-Finnish (FIN)

AF:

0.169

AC:

5436

AN:

32162

Middle Eastern (MID)

AF:

0.0954

AC:

386

AN:

4046

European-Non Finnish (NFE)

AF:

0.0779

AC:

30254

AN:

388238

Other (OTH)

AF:

0.113

AC:

3703

AN:

32724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

2763

5526

8289

11052

13815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.117

AC:

17735

AN:

152192

Hom.:

1248

Cov.:

AF XY:

0.123

AC XY:

9157

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.121

AC:

5032

AN:

41520

American (AMR)

AF:

0.142

AC:

2169

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0786

AC:

273

AN:

3472

East Asian (EAS)

AF:

0.307

AC:

1589

AN:

5182

South Asian (SAS)

AF:

0.193

AC:

929

AN:

4822

European-Finnish (FIN)

AF:

0.177

AC:

1877

AN:

10582

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0813

AC:

5529

AN:

68002

Other (OTH)

AF:

0.130

AC:

275

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

772

1544

2315

3087

3859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.0985

Hom.:

2212

Bravo

AF:

0.112

Asia WGS

AF:

0.221

AC:

766

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.12

(source)

DANN

Benign

0.59

PhyloP100

-1.5

Mutation Taster

=100/0

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