rs2866016

Positions:

• chr4-98583084-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005723.4(TSPAN5):​c.81+75062C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,098 control chromosomes in the GnomAD database, including 47,449 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 0.78 (47449 hom., cov: 32)
• Consequence: TSPAN5 NM_005723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN5	NM_005723.4	c.81+75062C>T		intron_variant		ENST00000305798.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN5	ENST00000305798.8	c.81+75062C>T		intron_variant		1	NM_005723.4	P1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119118 AN: 151980 Hom.: 47395 Cov.: 32

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.784 AC: 119237 AN: 152098 Hom.: 47449 Cov.: 32 AF XY: 0.786 AC XY: 58443 AN XY: 74332

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.754

Alfa AF: 0.736 Hom.: 31003

Bravo AF: 0.789

Asia WGS AF: 0.805 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.74

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: rs2866016; hg19: chr4-99504235;