17-8121440-C-A

Position:

• chr17-8121440-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001165967.2(HES7):​c.*131G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 610,010 control chromosomes in the GnomAD database, including 1,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (637 hom., cov: 32)
  • Exomes 𝑓: 0.022 (596 hom.)
• Consequence: HES7 NM_001165967.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.62

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 17-8121440-C-A is Benign according to our data. Variant chr17-8121440-C-A is described in ClinVar as [Benign]. Clinvar id is 1239596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HES7	NM_001165967.2	c.*131G>T		3_prime_UTR_variant	4/4	ENST00000541682.7
HES7	NM_032580.4	c.*131G>T		3_prime_UTR_variant	4/4
HES7	XM_047436940.1	c.*131G>T		3_prime_UTR_variant	3/3
HES7	XM_047436941.1	c.*131G>T		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HES7	ENST00000541682.7	c.*131G>T		3_prime_UTR_variant	4/4	1	NM_001165967.2	A1

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9409 AN: 152142 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0610

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00512

Gnomad OTH AF: 0.0497

GnomAD4 exome AF: 0.0220 AC: 10092 AN: 457750 Hom.: 596 Cov.: 6 AF XY: 0.0217 AC XY: 4910 AN XY: 226338

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0568

Gnomad4 ASJ exome AF: 0.0350

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.0557

Gnomad4 FIN exome AF: 0.0403

Gnomad4 NFE exome AF: 0.00347

Gnomad4 OTH exome AF: 0.0420

GnomAD4 genome AF: 0.0620 AC: 9433 AN: 152260 Hom.: 637 Cov.: 32 AF XY: 0.0644 AC XY: 4798 AN XY: 74466

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0476

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.0607

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.00512

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.00771 Hom.: 3

Bravo AF: 0.0676

Asia WGS AF: 0.159 AC: 551 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs114049508; hg19: chr17-8024758;