rs11178748

Positions:

• chr12-71341747-G-A
• chr12-71341747-G-T

Variant summary

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

The ENST00000393330.6(TSPAN8):​c.-275-58928C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 152,086 control chromosomes in the GnomAD database, including 1,113 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 0.097 (1113 hom., cov: 32)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 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.-275-58928C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14768 AN: 151968 Hom.: 1110 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.0891

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

GnomAD4 genome AF: 0.0972 AC: 14787 AN: 152086 Hom.: 1113 Cov.: 32 AF XY: 0.0942 AC XY: 7006 AN XY: 74346

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0631

Gnomad4 ASJ AF: 0.0482

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.0413

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.0546

Gnomad4 OTH AF: 0.0877

Alfa AF: 0.0583 Hom.: 361

Bravo AF: 0.103

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.35

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: rs11178748; hg19: chr12-71735527;