rs10506628

chr12-71395722-T-C

Variant summary

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

The ENST00000393330.6(TSPAN8):c.-276+45746A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 152,152 control chromosomes in the GnomAD database, including 789 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 0.082 (789 hom., cov: 32)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

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 (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN8	ENST00000393330.6	c.-276+45746A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12443 AN: 152034 Hom.: 787 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0680

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

GnomAD4 genome AF: 0.0818 AC: 12453 AN: 152152 Hom.: 789 Cov.: 32 AF XY: 0.0893 AC XY: 6641 AN XY: 74378

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.0665

Gnomad4 OTH AF: 0.0730

Alfa AF: 0.0682 Hom.: 539

Bravo AF: 0.0694

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.29
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10506628; hg19: chr12-71789502;