rs3817963

Positions:

• chr6-32400310-T-C

Variant summary

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

The NM_001304561.2(BTNL2):​c.730+1475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,034 control chromosomes in the GnomAD database, including 5,008 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 0.25 (5008 hom., cov: 31)
• Consequence: BTNL2 NM_001304561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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 (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL2	NM_001304561.2	c.730+1475A>G		intron_variant		ENST00000454136.8	NP_001291490.1
TSBP1-AS1	NR_136245.1	n.303-5144T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.730+1475A>G		intron_variant		5	NM_001304561.2	ENSP00000390613	P1
TSBP1-AS1	ENST00000645134.1	n.628-3359T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38069 AN: 151916 Hom.: 5010 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.250

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 38080 AN: 152034 Hom.: 5008 Cov.: 31 AF XY: 0.248 AC XY: 18467 AN XY: 74318

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.246

Alfa AF: 0.278 Hom.: 6997

Bravo AF: 0.262

Asia WGS AF: 0.244 AC: 849 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	2.9
DANN	Benign	0.55

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: rs3817963; hg19: chr6-32368087;