Genetic Variant HES7:p.Leu59Leu (chr17-8122394-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001165967.2(HES7):c.175T>C(p.Leu59Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,596,142 control chromosomes in the GnomAD database, including 13,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3220 hom., cov: 31)

Exomes 𝑓: 0.11 ( 10072 hom. )

Consequence

HES7
NM_001165967.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

HES7 (HGNC:15977): (hes family bHLH transcription factor 7) This gene encodes a member of the hairy and enhancer of split family of bHLH transcription factors. The mouse ortholog of this gene is regulated by Notch signaling. The protein functions as a transcriptional repressor, and is implicated in correct patterning of the axial skeleton. A mutation in this gene has been shown to result in spondylocostal dysostosis. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

HES7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 17-8122394-A-G is Benign according to our data. Variant chr17-8122394-A-G is described in ClinVar as [Benign]. Clinvar id is 262088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HES7	NM_001165967.2 link	c.175T>C	p.Leu59Leu	synonymous_variant	Exon 3 of 4	ENST00000541682.7	NP_001159439.1	Q9BYE0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HES7	ENST00000541682.7 link	c.175T>C	p.Leu59Leu	synonymous_variant	Exon 3 of 4	1	NM_001165967.2	ENSP00000446205.2	Q9BYE0-2
HES7	ENST00000317814.8 link	c.175T>C	p.Leu59Leu	synonymous_variant	Exon 3 of 4	1		ENSP00000314774.4	Q9BYE0-1
HES7	ENST00000577735.1 link	c.151T>C	p.Leu51Leu	synonymous_variant	Exon 4 of 5	3		ENSP00000462491.1	J3KSH6

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25848

AN:

151548

Hom.:

3196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.0781

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.0935

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.122

AC:

26518

AN:

217058

Hom.:

2067

AF XY:

0.123

AC XY:

14526

AN XY:

117722

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.0871

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.0812

Gnomad NFE exome

AF:

0.0949

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.108

AC:

156224

AN:

1444474

Hom.:

10072

Cov.:

AF XY:

0.110

AC XY:

78923

AN XY:

716796

show subpopulations

Gnomad4 AFR exome

AF:

0.354

Gnomad4 AMR exome

AF:

0.0925

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.0857

Gnomad4 NFE exome

AF:

0.0946

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.171

AC:

25916

AN:

151668

Hom.:

3220

Cov.:

AF XY:

0.170

AC XY:

12619

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.0781

Gnomad4 NFE

AF:

0.0936

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.119

Hom.:

1719

Bravo

AF:

0.181

Asia WGS

AF:

0.168

AC:

583

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over