12-71224423-C-T

Position:

• chr12-71224423-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393330.6(TSPAN8):​c.-110+52928G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,010 control chromosomes in the GnomAD database, including 43,664 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 (43664 hom., cov: 32)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN8	ENST00000393330.6	c.-110+52928G>A		intron_variant		1		P1
TSPAN8	ENST00000549421.1	n.206+58293G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114651 AN: 151892 Hom.: 43619 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.755 AC: 114760 AN: 152010 Hom.: 43664 Cov.: 32 AF XY: 0.754 AC XY: 56034 AN XY: 74272

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.708

Alfa AF: 0.717 Hom.: 65828

Bravo AF: 0.762

Asia WGS AF: 0.708 AC: 2460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.081
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs7306184; hg19: chr12-71618203;