rs1705232

Positions:

• chr12-71137309-G-A

Variant summary

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

The NM_004616.3(TSPAN8):​c.444+644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,800 control chromosomes in the GnomAD database, including 10,891 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 0.37 (10891 hom., cov: 31)
• Consequence: TSPAN8 NM_004616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN8	NM_004616.3	c.444+644C>T		intron_variant		ENST00000247829.8
TSPAN8	NM_001369760.1	c.444+644C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN8	ENST00000247829.8	c.444+644C>T		intron_variant		1	NM_004616.3	P1
TSPAN8	ENST00000393330.6	c.444+644C>T		intron_variant		1		P1
TSPAN8	ENST00000546561.2	c.444+644C>T		intron_variant		1		P1
TSPAN8	ENST00000552128.2	n.308+644C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55491 AN: 151680 Hom.: 10873 Cov.: 31

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00795

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.366 AC: 55548 AN: 151800 Hom.: 10891 Cov.: 31 AF XY: 0.358 AC XY: 26546 AN XY: 74202

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.00796

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.322

Alfa AF: 0.400 Hom.: 1541

Bravo AF: 0.360

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.41

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: rs1705232; hg19: chr12-71531089;