12-71128617-G-C

Variant names:

• chr12-71128617-G-C
• rs10506625
• NM_004616.3:c.660+714C>G

Variant summary

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

The NM_004616.3(TSPAN8):​c.660+714C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 150,704 control chromosomes in the GnomAD database, including 5,746 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 0.25 (5746 hom., cov: 31)
• Consequence: TSPAN8 NM_004616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3	c.660+714C>G		intron_variant	Intron 8 of 8	ENST00000247829.8	NP_004607.1
TSPAN8	NM_001369760.1	c.660+714C>G		intron_variant	Intron 7 of 7		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000247829.8	c.660+714C>G		intron_variant	Intron 8 of 8	1	NM_004616.3	ENSP00000247829.3
TSPAN8	ENST00000393330.6	c.660+714C>G		intron_variant	Intron 11 of 11	1		ENSP00000377003.2
TSPAN8	ENST00000546561.2	c.660+714C>G		intron_variant	Intron 7 of 7	1		ENSP00000447160.1
TSPAN8	ENST00000552128.2	n.524+714C>G		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38253 AN: 150606 Hom.: 5744 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00782

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.254 AC: 38256 AN: 150704 Hom.: 5746 Cov.: 31 AF XY: 0.250 AC XY: 18342 AN XY: 73476

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.00784

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.235

Alfa AF: 0.203 Hom.: 539

Bravo AF: 0.235

Asia WGS AF: 0.0880 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.59

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: rs10506625; hg19: chr12-71522397;