rs56066045

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001165967.2(HES7):c.402A>G(p.Lys134Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,564,774 control chromosomes in the GnomAD database, including 9,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1953 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7872 hom. )

Consequence

HES7
NM_001165967.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.763

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

spondylocostal dysostosis 4, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive spondylocostal dysostosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HES7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 17-8121862-T-C is Benign according to our data. Variant chr17-8121862-T-C is described in ClinVar as Benign. ClinVar VariationId is 262089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.763 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HES7	NM_001165967.2 link	c.402A>G	p.Lys134Lys	synonymous_variant	Exon 4 of 4	ENST00000541682.7	NP_001159439.1	Q9BYE0-2
HES7	NM_032580.4 link	c.387A>G	p.Lys129Lys	synonymous_variant	Exon 4 of 4		NP_115969.2	Q9BYE0-1
HES7	XM_047436940.1 link	c.498A>G	p.Lys166Lys	synonymous_variant	Exon 3 of 3		XP_047292896.1
HES7	XM_047436941.1 link	c.489A>G	p.Lys163Lys	synonymous_variant	Exon 5 of 5		XP_047292897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HES7	ENST00000541682.7 link	c.402A>G	p.Lys134Lys	synonymous_variant	Exon 4 of 4	1	NM_001165967.2	ENSP00000446205.2	Q9BYE0-2
HES7	ENST00000317814.8 link	c.387A>G	p.Lys129Lys	synonymous_variant	Exon 4 of 4	1		ENSP00000314774.4	Q9BYE0-1
HES7	ENST00000577735.1 link	c.378A>G	p.Lys126Lys	synonymous_variant	Exon 5 of 5	3		ENSP00000462491.1	J3KSH6

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21490

AN:

150386

Hom.:

1949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.0932

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0797

Gnomad MID

AF:

0.198

Gnomad NFE

AF:

0.0942

Gnomad OTH

AF:

0.141

GnomAD2 exomes

AF:

0.107

AC:

19914

AN:

185598

AF XY:

0.108

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.0814

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.0961

Gnomad FIN exome

AF:

0.0827

Gnomad NFE exome

AF:

0.0970

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.102

AC:

143561

AN:

1414282

Hom.:

7872

Cov.:

AF XY:

0.102

AC XY:

72025

AN XY:

703424

show subpopulations

African (AFR)

AF:

0.249

AC:

7358

AN:

29500

American (AMR)

AF:

0.0866

AC:

3620

AN:

41798

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4176

AN:

24738

East Asian (EAS)

AF:

0.0972

AC:

3512

AN:

36140

South Asian (SAS)

AF:

0.122

AC:

10144

AN:

83252

European-Finnish (FIN)

AF:

0.0872

AC:

3207

AN:

36766

Middle Eastern (MID)

AF:

0.168

AC:

770

AN:

4586

European-Non Finnish (NFE)

AF:

0.0947

AC:

104082

AN:

1098882

Other (OTH)

AF:

0.114

AC:

6692

AN:

58620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

8518

17035

25553

34070

42588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3980

7960

11940

15920

19900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.143

AC:

21507

AN:

150492

Hom.:

1953

Cov.:

AF XY:

0.142

AC XY:

10460

AN XY:

73532

show subpopulations

African (AFR)

AF:

0.253

AC:

10377

AN:

40992

American (AMR)

AF:

0.119

AC:

1802

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

577

AN:

3444

East Asian (EAS)

AF:

0.0934

AC:

476

AN:

5094

South Asian (SAS)

AF:

0.127

AC:

597

AN:

4704

European-Finnish (FIN)

AF:

0.0797

AC:

832

AN:

10434

Middle Eastern (MID)

AF:

0.203

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0942

AC:

6348

AN:

67366

Other (OTH)

AF:

0.140

AC:

293

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

969

1937

2906

3874

4843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.115

Hom.:

224

Bravo

AF:

0.150

Asia WGS

AF:

0.121

AC:

419

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Jun 09, 2021

GeneDx

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

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 03, 2018

Eurofins Ntd Llc (ga)

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

-0.61

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over