NM_012258.4:c.332-421A>G

Variant names:

• chr8-79766192-T-C
• rs2440624
• NM_012258.4:c.332-421A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_012258.4(HEY1):​c.332-421A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,529,534 control chromosomes in the GnomAD database, including 21,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1792 hom., cov: 33)
  • Exomes 𝑓: 0.17 (20012 hom.)
• Consequence: HEY1 NM_012258.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.231
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 8-79766192-T-C is Benign according to our data. Variant chr8-79766192-T-C is described in ClinVar as Benign. ClinVar VariationId is 1266917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012258.4. 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.332-421A>G		intron	N/A	NP_036390.3
	HEY1	NM_001040708.2		c.344-421A>G		intron	N/A	NP_001035798.1	Q9Y5J3-2
	HEY1	NM_001282851.2		c.61+11A>G		intron	N/A	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.332-421A>G		intron	N/A	ENSP00000346761.3	Q9Y5J3-1
	HEY1	ENST00000337919.9	TSL:1	c.344-421A>G		intron	N/A	ENSP00000338272.5	Q9Y5J3-2
	HEY1	ENST00000435063.4	TSL:1	n.142+175A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21195 AN: 152116 Hom.: 1787 Cov.: 33

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.0948

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.167 AC: 20875 AN: 124786 AF XY: 0.160

Gnomad AFR exome AF: 0.0379

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.166 AC: 228588 AN: 1377300 Hom.: 20012 Cov.: 30 AF XY: 0.164 AC XY: 111233 AN XY: 679632

African (AFR) AF: 0.0422 AC: 1323 AN: 31334

American (AMR) AF: 0.197 AC: 6873 AN: 34956

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4286 AN: 25010

East Asian (EAS) AF: 0.308 AC: 10987 AN: 35696

South Asian (SAS) AF: 0.0923 AC: 7207 AN: 78070

European-Finnish (FIN) AF: 0.196 AC: 6562 AN: 33424

Middle Eastern (MID) AF: 0.218 AC: 1238 AN: 5684

European-Non Finnish (NFE) AF: 0.168 AC: 180391 AN: 1075450

Other (OTH) AF: 0.169 AC: 9721 AN: 57676

GnomAD4 genome AF: 0.139 AC: 21212 AN: 152234 Hom.: 1792 Cov.: 33 AF XY: 0.137 AC XY: 10200 AN XY: 74422

African (AFR) AF: 0.0488 AC: 2027 AN: 41570

American (AMR) AF: 0.163 AC: 2493 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1511 AN: 5180

South Asian (SAS) AF: 0.0938 AC: 453 AN: 4828

European-Finnish (FIN) AF: 0.178 AC: 1887 AN: 10586

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11620 AN: 67986

Other (OTH) AF: 0.190 AC: 401 AN: 2112

Alfa AF: 0.127 Hom.: 1002

Bravo AF: 0.139

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.75
PhyloP100		0.23
PromoterAI		-0.00040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2440624; hg19: chr8-80678427; COSMIC: COSV104402006; COSMIC: COSV104402006;