8-79765887-G-A

Position:

• chr8-79765887-G-A

Variant summary

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

The NM_012258.4(HEY1):​c.332-116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 888,594 control chromosomes in the GnomAD database, including 8,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1418 hom., cov: 33)
  • Exomes 𝑓: 0.12 (6652 hom.)
• Consequence: HEY1 NM_012258.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.66

Genes affected

HEY1 (HGNC:4880): (hes related family bHLH transcription factor with YRPW motif 1) This gene encodes a nuclear protein belonging to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcriptional repressors. Expression of this gene is induced by the Notch and c-Jun signal transduction pathways. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-79765887-G-A is Benign according to our data. Variant chr8-79765887-G-A is described in ClinVar as [Benign]. Clinvar id is 1229713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEY1	NM_012258.4	c.332-116C>T		intron_variant		ENST00000354724.8	NP_036390.3
HEY1	NM_001040708.2	c.344-116C>T		intron_variant			NP_001035798.1
HEY1	NM_001282851.2	c.62-116C>T		intron_variant			NP_001269780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEY1	ENST00000354724.8	c.332-116C>T		intron_variant		1	NM_012258.4	ENSP00000346761.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19900 AN: 152132 Hom.: 1423 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.123 AC: 90752 AN: 736344 Hom.: 6652 AF XY: 0.128 AC XY: 47714 AN XY: 373524

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0796

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.000759

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.131 AC: 19895 AN: 152250 Hom.: 1418 Cov.: 33 AF XY: 0.133 AC XY: 9930 AN XY: 74442

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0951

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0595 Hom.: 88

Bravo AF: 0.122

Asia WGS AF: 0.113 AC: 393 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	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.56

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: rs57799278; hg19: chr8-80678122;