6-32393334-C-T

Position:

• chr6-32393334-C-T

Variant summary

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

The ENST00000426643.1(TSBP1-AS1):​n.373-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,492 control chromosomes in the GnomAD database, including 12,011 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 0.40 (11973 hom., cov: 32)
  • Exomes 𝑓: 0.41 (38 hom.)
• Consequence: TSBP1-AS1 ENST00000426643.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

Genes affected

TSBP1-AS1 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCG23	NR_044996.1	n.373-115C>T		intron_variant
TSBP1-AS1	NR_136245.1	n.303-12120C>T		intron_variant
BTNL2	NM_001304561.2	c.*62G>A		downstream_gene_variant		ENST00000454136.8	NP_001291490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8	c.*62G>A		downstream_gene_variant		5	NM_001304561.2	ENSP00000390613.3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60079 AN: 151896 Hom.: 11973 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.408 AC: 195 AN: 478 Hom.: 38 AF XY: 0.433 AC XY: 129 AN XY: 298

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.395 AC: 60098 AN: 152014 Hom.: 11973 Cov.: 32 AF XY: 0.397 AC XY: 29458 AN XY: 74294

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.387

Alfa AF: 0.409 Hom.: 22141

Bravo AF: 0.396

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3817973; hg19: chr6-32361111; COSMIC: COSV66631911;