rs2402056

Positions:

• chr7-116213449-A-C
• chr7-116213449-A-G
• chr7-116213449-A-T

Variant summary

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

The NM_015641.4(TES):​c.27+2715A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,062 control chromosomes in the GnomAD database, including 25,039 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 0.57 (25039 hom., cov: 33)
• Consequence: TES NM_015641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

Genes affected

TES (HGNC:14620): (testin LIM domain protein) Cancer-associated chromosomal changes often involve regions containing fragile sites. This gene maps to a common fragile site on chromosome 7q31.2 designated FRA7G. This gene is similar to mouse Testin, a testosterone-responsive gene encoding a Sertoli cell secretory protein containing three LIM domains. LIM domains are double zinc-finger motifs that mediate protein-protein interactions between transcription factors, cytoskeletal proteins and signaling proteins. This protein is a negative regulator of cell growth and may act as a tumor suppressor. This scaffold protein may also play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Multiple protein isoforms are encoded by transcript variants of this gene.[provided by RefSeq, Aug 2023]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TES	NM_015641.4	c.27+2715A>C		intron_variant		ENST00000358204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TES	ENST00000358204.9	c.27+2715A>C		intron_variant		1	NM_015641.4	P1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86355 AN: 151944 Hom.: 24989 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.569 AC: 86461 AN: 152062 Hom.: 25039 Cov.: 33 AF XY: 0.575 AC XY: 42740 AN XY: 74334

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.545

Alfa AF: 0.552 Hom.: 10478

Bravo AF: 0.567

Asia WGS AF: 0.711 AC: 2462 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.53

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: rs2402056; hg19: chr7-115853503;