rs4730720

Positions:

• chr7-116255181-T-C
• chr7-116255181-T-G

Variant summary

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

The NM_015641.4(TES):​c.1078-2113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,024 control chromosomes in the GnomAD database, including 8,436 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 0.33 (8436 hom., cov: 31)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: TES NM_015641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TES	NM_015641.4	c.1078-2113T>C		intron_variant		ENST00000358204.9	NP_056456.1
LOC124901730	XR_007060484.1	n.2124A>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TES	ENST00000358204.9	c.1078-2113T>C		intron_variant		1	NM_015641.4	ENSP00000350937	P1
	ENST00000444244.1	n.120A>G		non_coding_transcript_exon_variant	2/5	3
	ENST00000446355.2	n.204-11245A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49546 AN: 151898 Hom.: 8421 Cov.: 31

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.326 AC: 49608 AN: 152016 Hom.: 8436 Cov.: 31 AF XY: 0.333 AC XY: 24769 AN XY: 74310

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.298

Alfa AF: 0.304 Hom.: 1213

Bravo AF: 0.329

Asia WGS AF: 0.510 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.6
DANN	Benign	0.68

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: rs4730720; hg19: chr7-115895235;