4-98472597-G-A

Variant names:

• chr4-98472597-G-A
• rs75756375
• NM_005723.4:c.742-10C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005723.4(TSPAN5):​c.742-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,612,120 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (12 hom.)
• Consequence: TSPAN5 NM_005723.4 intron
• Scores: Splicing: ADA: 0.0005367
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 4-98472597-G-A is Benign according to our data. Variant chr4-98472597-G-A is described in ClinVar as [Benign]. Clinvar id is 710954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00765 (1165/152292) while in subpopulation AFR AF = 0.0268 (1112/41560). AF 95% confidence interval is 0.0255. There are 12 homozygotes in GnomAd4. There are 573 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN5	NM_005723.4	c.742-10C>T		intron_variant	Intron 7 of 7	ENST00000305798.8	NP_005714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN5	ENST00000305798.8	c.742-10C>T		intron_variant	Intron 7 of 7	1	NM_005723.4	ENSP00000307701.3
TSPAN5	ENST00000505184.5	c.529-10C>T		intron_variant	Intron 7 of 7	2		ENSP00000423916.1
TSPAN5	ENST00000508798.5	n.*96-10C>T		intron_variant	Intron 7 of 7	5		ENSP00000421808.1
TSPAN5	ENST00000511753.5	n.3820-10C>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.00764 AC: 1162 AN: 152174 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00209 AC: 521 AN: 249292 AF XY: 0.00156

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000796 AC: 1162 AN: 1459828 Hom.: 12 Cov.: 30 AF XY: 0.000673 AC XY: 489 AN XY: 726278

African (AFR) AF: 0.0291 AC: 973 AN: 33392

American (AMR) AF: 0.00139 AC: 62 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52786

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1110992

Other (OTH) AF: 0.00159 AC: 96 AN: 60324

GnomAD4 genome AF: 0.00765 AC: 1165 AN: 152292 Hom.: 12 Cov.: 32 AF XY: 0.00770 AC XY: 573 AN XY: 74456

African (AFR) AF: 0.0268 AC: 1112 AN: 41560

American (AMR) AF: 0.00242 AC: 37 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00927

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00054
dbscSNV1_RF	Benign	0.0020
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: rs75756375; hg19: chr4-99393748;