rs2270584

chr12-71138319-G-Achr12-71138319-G-Cchr12-71138319-G-T

Variant summary

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

The NM_004616.3(TSPAN8):c.262-89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,196,818 control chromosomes in the GnomAD database, including 86,299 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 0.32 (8494 hom., cov: 32)
  • Exomes 𝑓: 0.38 (77805 hom.)
• Consequence: TSPAN8 NM_004616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

Genes affected

TSPAN8 (HGNC:11855): (tetraspanin 8) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN8	NM_004616.3	c.262-89C>T		intron_variant		ENST00000247829.8
TSPAN8	NM_001369760.1	c.262-89C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN8	ENST00000247829.8	c.262-89C>T		intron_variant		1	NM_004616.3	P1
TSPAN8	ENST00000393330.6	c.262-89C>T		intron_variant		1		P1
TSPAN8	ENST00000546561.2	c.262-89C>T		intron_variant		1		P1
TSPAN8	ENST00000552128.2	n.126-89C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48205 AN: 151900 Hom.: 8490 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.379 AC: 396062 AN: 1044800 Hom.: 77805 AF XY: 0.378 AC XY: 201125 AN XY: 531454

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.317 AC: 48224 AN: 152018 Hom.: 8494 Cov.: 32 AF XY: 0.312 AC XY: 23222 AN XY: 74312

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.342

Alfa AF: 0.339 Hom.: 1592

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.0050
Dann	Benign	0.24

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: rs2270584; hg19: chr12-71532099; COSMIC: COSV56078889; COSMIC: COSV56078889;