rs1705236

Variant names:

• chr12-71151778-T-A
• rs1705236
• NM_004616.3:c.60+5841A>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.60+5841A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,260 control chromosomes in the GnomAD database, including 657 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 0.075 (657 hom., cov: 32)
• Consequence: TSPAN8 NM_004616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3	c.60+5841A>T		intron_variant	Intron 2 of 8	ENST00000247829.8	NP_004607.1
TSPAN8	NM_001369760.1	c.60+5841A>T		intron_variant	Intron 1 of 7		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000247829.8	c.60+5841A>T		intron_variant	Intron 2 of 8	1	NM_004616.3	ENSP00000247829.3
TSPAN8	ENST00000393330.6	c.60+5841A>T		intron_variant	Intron 5 of 11	1		ENSP00000377003.2
TSPAN8	ENST00000546561.2	c.60+5841A>T		intron_variant	Intron 1 of 7	1		ENSP00000447160.1
TSPAN8	ENST00000552786.1	n.319+5122A>T		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11382 AN: 152142 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0761

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

GnomAD4 genome AF: 0.0750 AC: 11416 AN: 152260 Hom.: 657 Cov.: 32 AF XY: 0.0730 AC XY: 5436 AN XY: 74448

African (AFR) AF: 0.146 AC: 6069 AN: 41546

American (AMR) AF: 0.0654 AC: 1000 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4828

European-Finnish (FIN) AF: 0.0157 AC: 167 AN: 10616

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0500 AC: 3400 AN: 68004

Other (OTH) AF: 0.0754 AC: 159 AN: 2110

Alfa AF: 0.0630 Hom.: 52

Bravo AF: 0.0816

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.74
PhyloP100		-0.038
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1705236; hg19: chr12-71545558;