12-71139430-C-T

Variant names:

• chr12-71139430-C-T
• rs11178648
• NM_004616.3:c.261+281G>A

Variant summary

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

The NM_004616.3(TSPAN8):​c.261+281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,804 control chromosomes in the GnomAD database, including 7,969 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 0.29 (7969 hom., cov: 40)
• Consequence: TSPAN8 NM_004616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 17 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3	c.261+281G>A		intron_variant	Intron 4 of 8	ENST00000247829.8	NP_004607.1
TSPAN8	NM_001369760.1	c.261+281G>A		intron_variant	Intron 3 of 7		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000247829.8	c.261+281G>A		intron_variant	Intron 4 of 8	1	NM_004616.3	ENSP00000247829.3
TSPAN8	ENST00000393330.6	c.261+281G>A		intron_variant	Intron 7 of 11	1		ENSP00000377003.2
TSPAN8	ENST00000546561.2	c.261+281G>A		intron_variant	Intron 3 of 7	1		ENSP00000447160.1
TSPAN8	ENST00000552128.2	n.-155G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44381 AN: 151684 Hom.: 7967 Cov.: 40

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.292 AC: 44379 AN: 151804 Hom.: 7969 Cov.: 40 AF XY: 0.289 AC XY: 21428 AN XY: 74208

African (AFR) AF: 0.0909 AC: 3772 AN: 41504

American (AMR) AF: 0.248 AC: 3791 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1482 AN: 3462

East Asian (EAS) AF: 0.306 AC: 1581 AN: 5168

South Asian (SAS) AF: 0.278 AC: 1343 AN: 4824

European-Finnish (FIN) AF: 0.334 AC: 3523 AN: 10534

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27635 AN: 67740

Other (OTH) AF: 0.322 AC: 678 AN: 2104

Alfa AF: 0.374 Hom.: 5245

Asia WGS AF: 0.255 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.72
PhyloP100		1.2
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: rs11178648; hg19: chr12-71533210;