rs1533104

Variant names:

• chr12-71262767-T-C
• rs1533104
• ENST00000393330.6:c.-110+14584A>G

Variant summary

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

The ENST00000393330.6(TSPAN8):​c.-110+14584A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,928 control chromosomes in the GnomAD database, including 28,540 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 0.60 (28540 hom., cov: 32)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 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+14584A>G		intron_variant	Intron 4 of 11	1		ENSP00000377003.2
TSPAN8	ENST00000549421.1	n.206+19949A>G		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91249 AN: 151810 Hom.: 28517 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.601 AC: 91311 AN: 151928 Hom.: 28540 Cov.: 32 AF XY: 0.591 AC XY: 43879 AN XY: 74242

African (AFR) AF: 0.644 AC: 26668 AN: 41424

American (AMR) AF: 0.478 AC: 7286 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1867 AN: 3470

East Asian (EAS) AF: 0.120 AC: 619 AN: 5160

South Asian (SAS) AF: 0.455 AC: 2188 AN: 4806

European-Finnish (FIN) AF: 0.621 AC: 6558 AN: 10558

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44231 AN: 67938

Other (OTH) AF: 0.552 AC: 1165 AN: 2110

Alfa AF: 0.620 Hom.: 50443

Bravo AF: 0.590

Asia WGS AF: 0.313 AC: 1090 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		-1.4
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: rs1533104; hg19: chr12-71656547; COSMIC: COSV66323185;