12-71128617-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004616.3. 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
	TSPAN8	NM_004616.3	MANE Select	c.660+714C>G		intron	N/A	NP_004607.1	P19075
	TSPAN8	NM_001369760.1		c.660+714C>G		intron	N/A	NP_001356689.1	P19075

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000247829.8	TSL:1 MANE Select	c.660+714C>G		intron	N/A	ENSP00000247829.3	P19075
	TSPAN8	ENST00000393330.6	TSL:1	c.660+714C>G		intron	N/A	ENSP00000377003.2	P19075
	TSPAN8	ENST00000546561.2	TSL:1	c.660+714C>G		intron	N/A	ENSP00000447160.1	P19075

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

African (AFR) AF: 0.143 AC: 5854 AN: 41074

American (AMR) AF: 0.212 AC: 3210 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3460

East Asian (EAS) AF: 0.00784 AC: 40 AN: 5104

South Asian (SAS) AF: 0.173 AC: 826 AN: 4784

European-Finnish (FIN) AF: 0.344 AC: 3481 AN: 10114

Middle Eastern (MID) AF: 0.214 AC: 62 AN: 290

European-Non Finnish (NFE) AF: 0.347 AC: 23499 AN: 67774

Other (OTH) AF: 0.235 AC: 489 AN: 2080

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.59
PhyloP100		0.16
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

Other links and lift over

dbSNP: rs10506625; hg19: chr12-71522397;