chr12-71137309-G-A

Variant names:

• chr12-71137309-G-A
• rs1705232
• NM_004616.3:c.444+644C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	NM_004616.3	MANE Select	c.444+644C>T		intron	N/A	NP_004607.1
	TSPAN8	NM_001369760.1		c.444+644C>T		intron	N/A	NP_001356689.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000247829.8	TSL:1 MANE Select	c.444+644C>T		intron	N/A	ENSP00000247829.3
	TSPAN8	ENST00000393330.6	TSL:1	c.444+644C>T		intron	N/A	ENSP00000377003.2
	TSPAN8	ENST00000546561.2	TSL:1	c.444+644C>T		intron	N/A	ENSP00000447160.1

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

African (AFR) AF: 0.424 AC: 17562 AN: 41378

American (AMR) AF: 0.284 AC: 4331 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3472

East Asian (EAS) AF: 0.00796 AC: 41 AN: 5148

South Asian (SAS) AF: 0.214 AC: 1028 AN: 4812

European-Finnish (FIN) AF: 0.357 AC: 3753 AN: 10524

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26945 AN: 67926

Other (OTH) AF: 0.322 AC: 679 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.41
PhyloP100		0.34
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: rs1705232; hg19: chr12-71531089;