Genetic Variant HES7:p.Gly213Gly (chr17-8121625-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1

The NM_001165967.2(HES7):c.639G>A(p.Gly213Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000308 in 1,313,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

HES7
NM_001165967.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.301

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 17-8121625-C-T is Benign according to our data. Variant chr17-8121625-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 763355.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.301 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000331 (385/1161796) while in subpopulation MID AF = 0.000619 (2/3230). AF 95% confidence interval is 0.000297. There are 0 homozygotes in GnomAdExome4. There are 188 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165967.2. 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
	HES7	NM_001165967.2	MANE Select	c.639G>A	p.Gly213Gly	synonymous	Exon 4 of 4	NP_001159439.1	Q9BYE0-2
	HES7	NM_032580.4		c.624G>A	p.Gly208Gly	synonymous	Exon 4 of 4	NP_115969.2	Q9BYE0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HES7	ENST00000541682.7	TSL:1 MANE Select	c.639G>A	p.Gly213Gly	synonymous	Exon 4 of 4	ENSP00000446205.2	Q9BYE0-2
HES7	ENST00000317814.8	TSL:1	c.624G>A	p.Gly208Gly	synonymous	Exon 4 of 4	ENSP00000314774.4	Q9BYE0-1
HES7	ENST00000577735.1	TSL:3	c.*179G>A		downstream_gene	N/A	ENSP00000462491.1	J3KSH6

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

534

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000331

AC:

385

AN:

1161796

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

188

AN XY:

557306

show subpopulations

African (AFR)

AF:

0.0000857

AC:

AN:

23324

American (AMR)

AF:

0.000227

AC:

AN:

8804

Ashkenazi Jewish (ASJ)

AF:

0.00296

AC:

AN:

15902

East Asian (EAS)

AF:

0.00

AC:

AN:

26974

South Asian (SAS)

AF:

0.0000260

AC:

AN:

38426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26178

Middle Eastern (MID)

AF:

0.000619

AC:

AN:

3230

European-Non Finnish (NFE)

AF:

0.000326

AC:

317

AN:

971154

Other (OTH)

AF:

0.000293

AC:

AN:

47804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000131

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41532

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67954

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.000193

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over