12-71151778-T-A

Position:

• chr12-71151778-T-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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/exons	MANE	Protein	UniProt
TSPAN8	NM_004616.3	c.60+5841A>T		intron_variant		ENST00000247829.8	NP_004607.1
TSPAN8	NM_001369760.1	c.60+5841A>T		intron_variant			NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000247829.8	c.60+5841A>T		intron_variant		1	NM_004616.3	ENSP00000247829	P1
TSPAN8	ENST00000393330.6	c.60+5841A>T		intron_variant		1		ENSP00000377003	P1
TSPAN8	ENST00000546561.2	c.60+5841A>T		intron_variant		1		ENSP00000447160	P1
TSPAN8	ENST00000552786.1	n.319+5122A>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0654

Gnomad4 ASJ AF: 0.0980

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0754

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1705236; hg19: chr12-71545558;