chr8-79766258-AGGCATGT-A

Variant names:

• chr8-79766258-AGGCATGT-A
• rs142613628
• NM_012258.4:c.331+386_331+392delACATGCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001282851.2(HEY1):​c.-2_5delACATGCC​(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,530,764 control chromosomes in the GnomAD database, including 11,511 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1270 hom., cov: 31)
  • Exomes 𝑓: 0.11 (10241 hom.)
• Consequence: HEY1 NM_001282851.2 frameshift, start_lost
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.792
• Publications: 3 publications found

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]

LINC01607 (HGNC:51660): (long intergenic non-protein coding RNA 1607)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-79766258-AGGCATGT-A is Benign according to our data. Variant chr8-79766258-AGGCATGT-A is described in ClinVar as Benign. ClinVar VariationId is 1232147.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282851.2. 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
	HEY1	NM_012258.4	MANE Select	c.331+386_331+392delACATGCC		intron	N/A	NP_036390.3
	HEY1	NM_001282851.2		c.-2_5delACATGCC	p.Met1fs	frameshift start_lost	Exon 1 of 2	NP_001269780.1	B4DEI9
	HEY1	NM_001282851.2		c.-2_5delACATGCC		5_prime_UTR	Exon 1 of 2	NP_001269780.1	B4DEI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEY1	ENST00000354724.8	TSL:1 MANE Select	c.331+386_331+392delACATGCC		intron	N/A	ENSP00000346761.3	Q9Y5J3-1
	HEY1	ENST00000337919.9	TSL:1	c.343+386_343+392delACATGCC		intron	N/A	ENSP00000338272.5	Q9Y5J3-2
	HEY1	ENST00000435063.4	TSL:1	n.142+102_142+108delACATGCC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18786 AN: 152010 Hom.: 1274 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.0733 AC: 8601 AN: 117348 AF XY: 0.0841

Gnomad AFR exome AF: 0.0507

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.000481

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0608

Gnomad OTH exome AF: 0.0774

GnomAD4 exome AF: 0.113 AC: 155102 AN: 1378634 Hom.: 10241 AF XY: 0.117 AC XY: 79646 AN XY: 680170

African (AFR) AF: 0.152 AC: 4775 AN: 31376

American (AMR) AF: 0.0671 AC: 2374 AN: 35356

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5096 AN: 25026

East Asian (EAS) AF: 0.000840 AC: 30 AN: 35730

South Asian (SAS) AF: 0.242 AC: 18919 AN: 78238

European-Finnish (FIN) AF: 0.124 AC: 4128 AN: 33412

Middle Eastern (MID) AF: 0.154 AC: 876 AN: 5680

European-Non Finnish (NFE) AF: 0.104 AC: 111703 AN: 1076084

Other (OTH) AF: 0.125 AC: 7201 AN: 57732

GnomAD4 genome AF: 0.123 AC: 18784 AN: 152130 Hom.: 1270 Cov.: 31 AF XY: 0.126 AC XY: 9375 AN XY: 74386

African (AFR) AF: 0.155 AC: 6424 AN: 41486

American (AMR) AF: 0.0898 AC: 1374 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5192

South Asian (SAS) AF: 0.244 AC: 1172 AN: 4802

European-Finnish (FIN) AF: 0.138 AC: 1457 AN: 10592

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7269 AN: 67976

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.122 Hom.: 235

Bravo AF: 0.116

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	HEY1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.79
Mutation Taster		=190/10	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs142613628; hg19: chr8-80678493; COSMIC: COSV61233341; COSMIC: COSV61233341;