rs10506626

chr12-71135711-G-A

Variant summary

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

The NM_004616.3(TSPAN8):c.444+2242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,958 control chromosomes in the GnomAD database, including 8,557 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 0.32 (8557 hom., cov: 30)
• Consequence: TSPAN8 NM_004616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN8	NM_004616.3	c.444+2242C>T		intron_variant		ENST00000247829.8
TSPAN8	NM_001369760.1	c.444+2242C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN8	ENST00000247829.8	c.444+2242C>T		intron_variant		1	NM_004616.3	P1
TSPAN8	ENST00000393330.6	c.444+2242C>T		intron_variant		1		P1
TSPAN8	ENST00000546561.2	c.444+2242C>T		intron_variant		1		P1
TSPAN8	ENST00000552128.2	n.308+2242C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48476 AN: 151840 Hom.: 8553 Cov.: 30

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.319 AC: 48495 AN: 151958 Hom.: 8557 Cov.: 30 AF XY: 0.314 AC XY: 23319 AN XY: 74230

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.343

Alfa AF: 0.341 Hom.: 1603

Bravo AF: 0.308

Asia WGS AF: 0.262 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.38

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: rs10506626; hg19: chr12-71529491;