12-71224423-C-T

Variant names:

• chr12-71224423-C-T
• rs7306184
• ENST00000393330.6:c.-110+52928G>A

Variant summary

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

The ENST00000393330.6(TSPAN8):​c.-110+52928G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,010 control chromosomes in the GnomAD database, including 43,664 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 0.75 (43664 hom., cov: 32)
• Consequence: TSPAN8 ENST00000393330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000393330.6	TSL:1	c.-110+52928G>A		intron	N/A	ENSP00000377003.2
	TSPAN8	ENST00000549421.1	TSL:3	n.206+58293G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114651 AN: 151892 Hom.: 43619 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.755 AC: 114760 AN: 152010 Hom.: 43664 Cov.: 32 AF XY: 0.754 AC XY: 56034 AN XY: 74272

African (AFR) AF: 0.836 AC: 34696 AN: 41494

American (AMR) AF: 0.778 AC: 11864 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2423 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3548 AN: 5136

South Asian (SAS) AF: 0.645 AC: 3108 AN: 4816

European-Finnish (FIN) AF: 0.790 AC: 8363 AN: 10582

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48422 AN: 67948

Other (OTH) AF: 0.708 AC: 1489 AN: 2102

Alfa AF: 0.725 Hom.: 152715

Bravo AF: 0.762

Asia WGS AF: 0.708 AC: 2460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.081
DANN	Benign	0.49
PhyloP100		-1.7
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: rs7306184; hg19: chr12-71618203;