dbSNP rs4730720: TES:c.1078-2113T>C (chr7-116255181-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0760

Publications

6 publications found

Variant links:

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]

TES links:

ENSG00000243243 (HGNC:):

ENSG00000243243 links:

CAV2-DT (HGNC:40129):

CAV2-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TES	NM_015641.4	MANE Select	c.1078-2113T>C		intron	N/A	NP_056456.1	A4D0U5
	TES	NM_152829.3		c.1051-2113T>C		intron	N/A	NP_690042.1	Q9UGI8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TES	ENST00000358204.9	TSL:1 MANE Select	c.1078-2113T>C	intron	N/A	ENSP00000350937.4	Q9UGI8-1
TES	ENST00000393481.6	TSL:1	c.1051-2113T>C	intron	N/A	ENSP00000377121.2	Q9UGI8-2
TES	ENST00000496912.1	TSL:1	n.629-2113T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49546

AN:

151898

Hom.:

8421

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.326

AC:

49608

AN:

152016

Hom.:

8436

Cov.:

AF XY:

0.333

AC XY:

24769

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.402

AC:

16652

AN:

41436

American (AMR)

AF:

0.322

AC:

4916

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

920

AN:

3472

East Asian (EAS)

AF:

0.577

AC:

2984

AN:

5172

South Asian (SAS)

AF:

0.354

AC:

1709

AN:

4826

European-Finnish (FIN)

AF:

0.331

AC:

3489

AN:

10532

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

18014

AN:

67978

Other (OTH)

AF:

0.298

AC:

630

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1691

3381

5072

6762

8453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.308

Hom.:

1287

Bravo

AF:

0.329

Asia WGS

AF:

0.510

AC:

1766

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

5.6

(source)

DANN

Benign

0.68

PhyloP100

0.076

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over