rs10506627

Variant names:

• chr12-71272772-T-C
• rs10506627
• ENST00000393330.6:c.-110+4579A>G

Variant summary

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

The ENST00000393330.6(TSPAN8):​c.-110+4579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,926 control chromosomes in the GnomAD database, including 1,287 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 0.12 (1287 hom., cov: 31)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393330.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000393330.6	TSL:1	c.-110+4579A>G		intron	N/A	ENSP00000377003.2	P19075
	TSPAN8	ENST00000549421.1	TSL:3	n.206+9944A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17651 AN: 151808 Hom.: 1286 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0951

Gnomad OTH AF: 0.0913

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

GnomAD4 genome AF: 0.116 AC: 17656 AN: 151926 Hom.: 1287 Cov.: 31 AF XY: 0.124 AC XY: 9205 AN XY: 74246

African (AFR) AF: 0.106 AC: 4407 AN: 41484

American (AMR) AF: 0.151 AC: 2291 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3472

East Asian (EAS) AF: 0.282 AC: 1453 AN: 5154

South Asian (SAS) AF: 0.0604 AC: 291 AN: 4820

European-Finnish (FIN) AF: 0.223 AC: 2353 AN: 10554

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0951 AC: 6458 AN: 67930

Other (OTH) AF: 0.0903 AC: 190 AN: 2104

Alfa AF: 0.0942 Hom.: 1431

Bravo AF: 0.113

Asia WGS AF: 0.161 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.062
DANN	Benign	0.45
PhyloP100		-3.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10506627;

hg19: chr12-71666552;

COSMIC: COSV107507610;