12-71262943-C-T

Variant names:

• chr12-71262943-C-T
• rs6581998
• ENST00000393330.6:c.-110+14408G>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+14408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,074 control chromosomes in the GnomAD database, including 47,135 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 0.78 (47135 hom., cov: 32)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 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+14408G>A		intron_variant	Intron 4 of 11	1		ENSP00000377003.2
TSPAN8	ENST00000549421.1	n.206+19773G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118963 AN: 151956 Hom.: 47086 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.783 AC: 119077 AN: 152074 Hom.: 47135 Cov.: 32 AF XY: 0.783 AC XY: 58222 AN XY: 74326

African (AFR) AF: 0.900 AC: 37367 AN: 41516

American (AMR) AF: 0.791 AC: 12049 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2439 AN: 3470

East Asian (EAS) AF: 0.774 AC: 4004 AN: 5172

South Asian (SAS) AF: 0.670 AC: 3232 AN: 4824

European-Finnish (FIN) AF: 0.811 AC: 8565 AN: 10566

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.721 AC: 49013 AN: 67974

Other (OTH) AF: 0.732 AC: 1546 AN: 2112

Alfa AF: 0.787 Hom.: 7000

Bravo AF: 0.792

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.74
PhyloP100		0.10
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: rs6581998; hg19: chr12-71656723;