Variant 17-8123046-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001165967.2(HES7):c.123G>A(p.Glu41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 1,600,464 control chromosomes in the GnomAD database, including 9,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 1009 hom., cov: 32)

Exomes 𝑓: 0.060 ( 8278 hom. )

Consequence

HES7
NM_001165967.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.748

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 17-8123046-C-T is Benign according to our data. Variant chr17-8123046-C-T is described in ClinVar as [Benign]. Clinvar id is 262087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8123046-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HES7	NM_001165967.2 linkuse as main transcript	c.123G>A	p.Glu41=	synonymous_variant	2/4	ENST00000541682.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HES7	ENST00000541682.7 linkuse as main transcript	c.123G>A	p.Glu41=	synonymous_variant	2/4	1	NM_001165967.2	A1	Q9BYE0-2
HES7	ENST00000317814.8 linkuse as main transcript	c.123G>A	p.Glu41=	synonymous_variant	2/4	1		P4	Q9BYE0-1
HES7	ENST00000577735.1 linkuse as main transcript	c.99G>A	p.Glu33=	synonymous_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.0664

AC:

10093

AN:

152094

Hom.:

998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.0804

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.0858

Gnomad FIN

AF:

0.0506

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0389

Gnomad OTH

AF:

0.0814

GnomAD3 exomes

AF:

0.119

AC:

26489

AN:

221932

Hom.:

3955

AF XY:

0.106

AC XY:

12900

AN XY:

121718

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.0855

Gnomad EAS exome

AF:

0.374

Gnomad SAS exome

AF:

0.0731

Gnomad FIN exome

AF:

0.0552

Gnomad NFE exome

AF:

0.0366

Gnomad OTH exome

AF:

0.0965

GnomAD4 exome

AF:

0.0600

AC:

86958

AN:

1448252

Hom.:

8278

Cov.:

AF XY:

0.0593

AC XY:

42695

AN XY:

719442

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.0880

Gnomad4 EAS exome

AF:

0.430

Gnomad4 SAS exome

AF:

0.0712

Gnomad4 FIN exome

AF:

0.0512

Gnomad4 NFE exome

AF:

0.0352

Gnomad4 OTH exome

AF:

0.0700

GnomAD4 genome

AF:

0.0665

AC:

10115

AN:

152212

Hom.:

1009

Cov.:

AF XY:

0.0723

AC XY:

5380

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.0804

Gnomad4 EAS

AF:

0.378

Gnomad4 SAS

AF:

0.0856

Gnomad4 FIN

AF:

0.0506

Gnomad4 NFE

AF:

0.0389

Gnomad4 OTH

AF:

0.0853

Alfa

AF:

0.0449

Hom.:

136

Bravo

AF:

0.0790

Asia WGS

AF:

0.190

AC:

659

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.96

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

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