4-98586685-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005723.4(TSPAN5):c.81+71461G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0904 in 152,164 control chromosomes in the GnomAD database, including 737 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 0.090 (737 hom., cov: 33)
• Consequence: TSPAN5 NM_005723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

Genes affected

TSPAN5 (HGNC:17753): (tetraspanin 5) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN5	NM_005723.4	c.81+71461G>A		intron_variant		ENST00000305798.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN5	ENST00000305798.8	c.81+71461G>A		intron_variant		1	NM_005723.4	P1

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13758 AN: 152046 Hom.: 736 Cov.: 33

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0904 AC: 13762 AN: 152164 Hom.: 737 Cov.: 33 AF XY: 0.0912 AC XY: 6784 AN XY: 74382

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0485 Hom.: 54

Bravo AF: 0.0865

Asia WGS AF: 0.199 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	16
Dann	Benign	0.69

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: rs10489125; hg19: chr4-99507836;