rs17202456

Positions:

• chr6-32395997-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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]

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

ACMG classification

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/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.1078+42C>T		intron_variant		ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.303-9457G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.1078+42C>T		intron_variant		5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.627+5244G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21203 AN: 152078 Hom.: 1609 Cov.: 32

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

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.: 20 AF XY: 0.136 AC XY: 88587 AN XY: 652094

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.: 32 AF XY: 0.143 AC XY: 10629 AN XY: 74404

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

Other links and lift over

dbSNP: rs17202456; hg19: chr6-32363774; COSMIC: COSV66632212; COSMIC: COSV66632212;