rs2270584

Variant names:

• chr12-71138319-G-A
• rs2270584
• NM_004616.3:c.262-89C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-71138319-G-A
• chr12-71138319-G-C
• chr12-71138319-G-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.262-89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,196,818 control chromosomes in the GnomAD database, including 86,299 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 0.32 (8494 hom., cov: 32)
  • Exomes 𝑓: 0.38 (77805 hom.)
• Consequence: TSPAN8 NM_004616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	NM_004616.3	MANE Select	c.262-89C>T		intron	N/A	NP_004607.1	P19075
	TSPAN8	NM_001369760.1		c.262-89C>T		intron	N/A	NP_001356689.1	P19075

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000247829.8	TSL:1 MANE Select	c.262-89C>T		intron	N/A	ENSP00000247829.3	P19075
	TSPAN8	ENST00000393330.6	TSL:1	c.262-89C>T		intron	N/A	ENSP00000377003.2	P19075
	TSPAN8	ENST00000546561.2	TSL:1	c.262-89C>T		intron	N/A	ENSP00000447160.1	P19075

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48205 AN: 151900 Hom.: 8490 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.379 AC: 396062 AN: 1044800 Hom.: 77805 AF XY: 0.378 AC XY: 201125 AN XY: 531454

African (AFR) AF: 0.165 AC: 3997 AN: 24212

American (AMR) AF: 0.194 AC: 6498 AN: 33480

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 8708 AN: 19836

East Asian (EAS) AF: 0.311 AC: 11641 AN: 37438

South Asian (SAS) AF: 0.289 AC: 19663 AN: 67940

European-Finnish (FIN) AF: 0.356 AC: 17661 AN: 49678

Middle Eastern (MID) AF: 0.391 AC: 1842 AN: 4708

European-Non Finnish (NFE) AF: 0.406 AC: 309257 AN: 761474

Other (OTH) AF: 0.365 AC: 16795 AN: 46034

GnomAD4 genome AF: 0.317 AC: 48224 AN: 152018 Hom.: 8494 Cov.: 32 AF XY: 0.312 AC XY: 23222 AN XY: 74312

African (AFR) AF: 0.173 AC: 7168 AN: 41502

American (AMR) AF: 0.258 AC: 3939 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1547 AN: 3464

East Asian (EAS) AF: 0.305 AC: 1572 AN: 5162

South Asian (SAS) AF: 0.279 AC: 1344 AN: 4810

European-Finnish (FIN) AF: 0.336 AC: 3544 AN: 10554

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27807 AN: 67946

Other (OTH) AF: 0.342 AC: 721 AN: 2108

Alfa AF: 0.334 Hom.: 1605

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0050
DANN	Benign	0.24
PhyloP100		-2.4
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: rs2270584;

hg19: chr12-71532099;

COSMIC: COSV56078889;

COSMIC: COSV56078889;