chr12-71241014-A-G

Variant names:

• chr12-71241014-A-G
• rs4760790
• ENST00000393330.6:c.-110+36337T>C

Variant summary

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

The ENST00000393330.6(TSPAN8):​c.-110+36337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,042 control chromosomes in the GnomAD database, including 44,398 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 0.76 (44398 hom., cov: 31)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 42 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 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+36337T>C		intron	N/A	ENSP00000377003.2	P19075
	TSPAN8	ENST00000549421.1	TSL:3	n.206+41702T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115600 AN: 151924 Hom.: 44350 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.761 AC: 115711 AN: 152042 Hom.: 44398 Cov.: 31 AF XY: 0.761 AC XY: 56593 AN XY: 74332

African (AFR) AF: 0.842 AC: 34929 AN: 41474

American (AMR) AF: 0.780 AC: 11905 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3898 AN: 5154

South Asian (SAS) AF: 0.664 AC: 3203 AN: 4826

European-Finnish (FIN) AF: 0.801 AC: 8486 AN: 10596

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48493 AN: 67942

Other (OTH) AF: 0.717 AC: 1515 AN: 2112

Alfa AF: 0.728 Hom.: 125086

Bravo AF: 0.768

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.58
DANN	Benign	0.63
PhyloP100		-0.59
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: rs4760790;

hg19: chr12-71634794;