7-116226300-A-G

Variant names:

• chr7-116226300-A-G
• rs1881287
• NM_015641.4:c.28-8234A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015641.4(TES):​c.28-8234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,128 control chromosomes in the GnomAD database, including 8,923 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 (8923 hom., cov: 32)
• Consequence: TES NM_015641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TES	NM_015641.4	MANE Select	c.28-8234A>G		intron	N/A	NP_056456.1
	TES	NM_152829.3		c.-1+3274A>G		intron	N/A	NP_690042.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TES	ENST00000358204.9	TSL:1 MANE Select	c.28-8234A>G		intron	N/A	ENSP00000350937.4
	TES	ENST00000393481.6	TSL:1	c.-1+3274A>G		intron	N/A	ENSP00000377121.2
	TES	ENST00000485009.1	TSL:1	n.76+3274A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50713 AN: 152010 Hom.: 8891 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.334 AC: 50802 AN: 152128 Hom.: 8923 Cov.: 32 AF XY: 0.340 AC XY: 25273 AN XY: 74376

African (AFR) AF: 0.435 AC: 18036 AN: 41490

American (AMR) AF: 0.294 AC: 4497 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2951 AN: 5170

South Asian (SAS) AF: 0.353 AC: 1703 AN: 4818

European-Finnish (FIN) AF: 0.333 AC: 3526 AN: 10592

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18224 AN: 67986

Other (OTH) AF: 0.303 AC: 640 AN: 2112

Alfa AF: 0.168 Hom.: 312

Bravo AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.59
PhyloP100		-1.1
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: rs1881287; hg19: chr7-115866354;