chr17-8121646-C-T

Position:

• chr17-8121646-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001165967.2(HES7):​c.618G>A​(p.Pro206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000497 in 1,167,762 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: not found (cov: 33)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: HES7 NM_001165967.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.115

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 17-8121646-C-T is Benign according to our data. Variant chr17-8121646-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 752251.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.115 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HES7	NM_001165967.2	c.618G>A	p.Pro206=	synonymous_variant	4/4	ENST00000541682.7
HES7	NM_032580.4	c.603G>A	p.Pro201=	synonymous_variant	4/4
HES7	XM_047436940.1	c.714G>A	p.Pro238=	synonymous_variant	3/3
HES7	XM_047436941.1	c.705G>A	p.Pro235=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HES7	ENST00000541682.7	c.618G>A	p.Pro206=	synonymous_variant	4/4	1	NM_001165967.2	A1
HES7	ENST00000317814.8	c.603G>A	p.Pro201=	synonymous_variant	4/4	1		P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000497 AC: 58 AN: 1167762 Hom.: 0 Cov.: 30 AF XY: 0.0000499 AC XY: 28 AN XY: 560954

Gnomad4 AFR exome AF: 0.0000428

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000249

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000575

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.95

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

Other links and lift over

dbSNP: rs1234263226; hg19: chr17-8024964;