rs3763308

chr6-32406863-G-Achr6-32406863-G-T

Variant summary

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

The NM_001304561.2(BTNL2):c.79+182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 548,702 control chromosomes in the GnomAD database, including 1,026 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 0.066 (403 hom., cov: 32)
  • Exomes 𝑓: 0.049 (623 hom.)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL2	NM_001304561.2	c.79+182C>T		intron_variant		ENST00000454136.8
TSBP1-AS1	NR_136245.1	n.1153G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL2	ENST00000454136.8	c.79+182C>T		intron_variant		5	NM_001304561.2	P1
TSBP1-AS1	ENST00000645134.1	n.1602G>A		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9987 AN: 152076 Hom.: 403 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0487 AC: 19293 AN: 396508 Hom.: 623 Cov.: 4 AF XY: 0.0485 AC XY: 10100 AN XY: 208192

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0885

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.0354

Gnomad4 SAS exome AF: 0.0543

Gnomad4 FIN exome AF: 0.0680

Gnomad4 NFE exome AF: 0.0425

Gnomad4 OTH exome AF: 0.0495

GnomAD4 genome AF: 0.0656 AC: 9988 AN: 152194 Hom.: 403 Cov.: 32 AF XY: 0.0659 AC XY: 4901 AN XY: 74424

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0726

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.0265

Gnomad4 SAS AF: 0.0502

Gnomad4 FIN AF: 0.0698

Gnomad4 NFE AF: 0.0428

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0421 Hom.: 233

Bravo AF: 0.0681

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.7
Dann	Benign	0.33

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: rs3763308; hg19: chr6-32374640;