12-71312516-G-T

Variant names:

• chr12-71312516-G-T
• rs7964431
• ENST00000393330.6:c.-275-29697C>A

Variant summary

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

The ENST00000393330.6(TSPAN8):​c.-275-29697C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,112 control chromosomes in the GnomAD database, including 46,923 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 (46923 hom., cov: 32)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 1 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]

LOC105369832 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369832	XR_001749199.1	n.47+2807C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000393330.6	c.-275-29697C>A		intron_variant	Intron 2 of 11	1		ENSP00000377003.2
TSPAN8	ENST00000549421.1	n.102+2807C>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118846 AN: 151992 Hom.: 46872 Cov.: 32

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.782 AC: 118954 AN: 152112 Hom.: 46923 Cov.: 32 AF XY: 0.788 AC XY: 58589 AN XY: 74354

African (AFR) AF: 0.863 AC: 35810 AN: 41516

American (AMR) AF: 0.779 AC: 11913 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2329 AN: 3466

East Asian (EAS) AF: 0.991 AC: 5136 AN: 5182

South Asian (SAS) AF: 0.878 AC: 4235 AN: 4822

European-Finnish (FIN) AF: 0.806 AC: 8513 AN: 10560

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48496 AN: 67966

Other (OTH) AF: 0.758 AC: 1600 AN: 2112

Alfa AF: 0.755 Hom.: 5309

Bravo AF: 0.783

Asia WGS AF: 0.901 AC: 3132 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.7
DANN	Benign	0.29
PhyloP100		0.26
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: rs7964431; hg19: chr12-71706296;