rs10506628

Variant names:

• chr12-71395722-T-C
• rs10506628
• ENST00000393330.6:c.-276+45746A>G

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000393330.6	c.-276+45746A>G		intron_variant	Intron 2 of 11	1		ENSP00000377003.2

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;