17-8121685-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_001165967.2(HES7):​c.579C>A​(p.Gly193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000761 in 1,326,652 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

HES7
NM_001165967.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.874
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 17-8121685-G-T is Benign according to our data. Variant chr17-8121685-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1532977.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.874 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000817 (96/1174528) while in subpopulation SAS AF= 0.00185 (80/43324). AF 95% confidence interval is 0.00152. There are 0 homozygotes in gnomad4_exome. There are 64 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HES7NM_001165967.2 linkuse as main transcriptc.579C>A p.Gly193= synonymous_variant 4/4 ENST00000541682.7
HES7NM_032580.4 linkuse as main transcriptc.564C>A p.Gly188= synonymous_variant 4/4
HES7XM_047436940.1 linkuse as main transcriptc.675C>A p.Gly225= synonymous_variant 3/3
HES7XM_047436941.1 linkuse as main transcriptc.666C>A p.Gly222= synonymous_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HES7ENST00000541682.7 linkuse as main transcriptc.579C>A p.Gly193= synonymous_variant 4/41 NM_001165967.2 A1Q9BYE0-2
HES7ENST00000317814.8 linkuse as main transcriptc.564C>A p.Gly188= synonymous_variant 4/41 P4Q9BYE0-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152124
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000397
AC:
1
AN:
2522
Hom.:
0
AF XY:
0.000658
AC XY:
1
AN XY:
1520
show subpopulations
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 SAS exome
AF:
0.00355
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000817
AC:
96
AN:
1174528
Hom.:
0
Cov.:
30
AF XY:
0.000113
AC XY:
64
AN XY:
564358
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000102
Gnomad4 OTH exome
AF:
0.000124
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152124
Hom.:
0
Cov.:
33
AF XY:
0.0000673
AC XY:
5
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
Asia WGS
AF:
0.000290
AC:
1
AN:
3460

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMay 22, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
10
DANN
Benign
0.92

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.

Other links and lift over

dbSNP: rs759681801; hg19: chr17-8025003; API