4-98586685-C-T

Variant names:

• chr4-98586685-C-T
• rs10489125
• NM_005723.4:c.81+71461G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005723.4. 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
	TSPAN5	NM_005723.4	MANE Select	c.81+71461G>A		intron	N/A	NP_005714.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN5	ENST00000305798.8	TSL:1 MANE Select	c.81+71461G>A		intron	N/A	ENSP00000307701.3	P62079
	TSPAN5	ENST00000935829.1		c.81+71461G>A		intron	N/A	ENSP00000605888.1
	TSPAN5	ENST00000951778.1		c.81+71461G>A		intron	N/A	ENSP00000621837.1

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

African (AFR) AF: 0.0578 AC: 2400 AN: 41516

American (AMR) AF: 0.0879 AC: 1343 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3470

East Asian (EAS) AF: 0.124 AC: 639 AN: 5170

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4818

European-Finnish (FIN) AF: 0.0678 AC: 718 AN: 10586

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6994 AN: 68002

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.0486 Hom.: 55

Bravo AF: 0.0865

Asia WGS AF: 0.199 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.69
PhyloP100		-0.56
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

Other links and lift over

dbSNP: rs10489125; hg19: chr4-99507836;