dbSNP rs17202456: BTNL2:c.1078+42C>T (chr6-32395997-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001304561.2(BTNL2):c.1078+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,469,812 control chromosomes in the GnomAD database, including 15,162 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 0.14 ( 1609 hom., cov: 32)

Exomes 𝑓: 0.14 ( 13553 hom. )

Consequence

BTNL2
NM_001304561.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.341

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL2	NM_001304561.2 link	c.1078+42C>T		intron_variant	Intron 5 of 7	ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4
TSBP1-AS1	NR_136245.1 link	n.303-9457G>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.1078+42C>T		intron_variant	Intron 5 of 7	5	NM_001304561.2	ENSP00000390613.3		F8WBA1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21203

AN:

152078

Hom.:

1609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0435

Gnomad SAS

AF:

0.0855

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.134

AC:

27924

AN:

208808

Hom.:

2200

AF XY:

0.132

AC XY:

14843

AN XY:

112764

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.0315

Gnomad EAS exome

AF:

0.0468

Gnomad SAS exome

AF:

0.0884

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.138

AC:

181768

AN:

1317616

Hom.:

13553

Cov.:

AF XY:

0.136

AC XY:

88587

AN XY:

652094

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.0329

Gnomad4 EAS exome

AF:

0.0747

Gnomad4 SAS exome

AF:

0.0891

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.139

AC:

21206

AN:

152196

Hom.:

1609

Cov.:

AF XY:

0.143

AC XY:

10629

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.0432

Gnomad4 SAS

AF:

0.0856

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.126

Hom.:

474

Bravo

AF:

0.127

Asia WGS

AF:

0.0730

AC:

256

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.9

DANN

Benign

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over