rs7961581

Variant names:

• chr12-71269322-C-T
• rs7961581
• ENST00000393330.6:c.-110+8029G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393330.6(TSPAN8):​c.-110+8029G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 151,922 control chromosomes in the GnomAD database, including 42,953 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 0.75 (42953 hom., cov: 32)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 223 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 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.-110+8029G>A		intron_variant	Intron 4 of 11	1		ENSP00000377003.2
TSPAN8	ENST00000549421.1	n.206+13394G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113857 AN: 151804 Hom.: 42921 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.750 AC: 113950 AN: 151922 Hom.: 42953 Cov.: 32 AF XY: 0.751 AC XY: 55762 AN XY: 74218

African (AFR) AF: 0.796 AC: 33023 AN: 41476

American (AMR) AF: 0.778 AC: 11826 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3470

East Asian (EAS) AF: 0.776 AC: 3992 AN: 5144

South Asian (SAS) AF: 0.669 AC: 3224 AN: 4820

European-Finnish (FIN) AF: 0.793 AC: 8390 AN: 10574

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48759 AN: 67916

Other (OTH) AF: 0.711 AC: 1501 AN: 2110

Alfa AF: 0.728 Hom.: 164381

Bravo AF: 0.754

Asia WGS AF: 0.744 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.021
DANN	Benign	0.71
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7961581; hg19: chr12-71663102;