chr12-71166082-G-C

Variant names:

• chr12-71166082-G-C
• rs4500567
• ENST00000393330.6:c.-109-8295C>G

Variant summary

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

The ENST00000393330.6(TSPAN8):​c.-109-8295C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 152,210 control chromosomes in the GnomAD database, including 757 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 0.062 (757 hom., cov: 33)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.306 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.-109-8295C>G		intron_variant	Intron 4 of 11	1		ENSP00000377003.2
TSPAN8	ENST00000549421.1	n.207-8295C>G		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9497 AN: 152092 Hom.: 749 Cov.: 33

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0922

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

GnomAD4 genome AF: 0.0625 AC: 9513 AN: 152210 Hom.: 757 Cov.: 33 AF XY: 0.0660 AC XY: 4911 AN XY: 74416

African (AFR) AF: 0.0433 AC: 1797 AN: 41540

American (AMR) AF: 0.184 AC: 2813 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3472

East Asian (EAS) AF: 0.319 AC: 1641 AN: 5152

South Asian (SAS) AF: 0.105 AC: 506 AN: 4816

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0266 AC: 1808 AN: 68012

Other (OTH) AF: 0.0950 AC: 201 AN: 2116

Alfa AF: 0.0405 Hom.: 43

Bravo AF: 0.0797

Asia WGS AF: 0.243 AC: 841 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	7.6
DANN	Benign	0.29
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs4500567; hg19: chr12-71559862;