4-74382717-A-G

Variant names:

• chr4-74382717-A-G
• rs2367707
• NM_001432.3:c.351A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001432.3(EREG):​c.351A>G​(p.Glu117Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,612,664 control chromosomes in the GnomAD database, including 502,511 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47905 hom., cov: 33)
  • Exomes 𝑓: 0.79 (454606 hom.)
• Consequence: EREG NM_001432.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 26 publications found

Genes affected

EREG (HGNC:3443): (epiregulin) This gene encodes a secreted peptide hormone and member of the epidermal growth factor (EGF) family of proteins. The encoded protein is a ligand of the epidermal growth factor receptor (EGFR) and the structurally related erb-b2 receptor tyrosine kinase 4 (ERBB4). The encoded protein may be involved in a wide range of biological processes including inflammation, wound healing, oocyte maturation, and cell proliferation. Additionally, the encoded protein may promote the progression of cancers of various human tissues. [provided by RefSeq, Jul 2015]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001432.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EREG	NM_001432.3	MANE Select	c.351A>G	p.Glu117Glu	synonymous	Exon 4 of 5	NP_001423.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EREG	ENST00000244869.3	TSL:1 MANE Select	c.351A>G	p.Glu117Glu	synonymous	Exon 4 of 5	ENSP00000244869.2
	EREG	ENST00000503689.1	TSL:2	n.295A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120497 AN: 152092 Hom.: 47863 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.808

GnomAD2 exomes AF: 0.794 AC: 199453 AN: 251048 AF XY: 0.790

Gnomad AFR exome AF: 0.774

Gnomad AMR exome AF: 0.870

Gnomad ASJ exome AF: 0.808

Gnomad EAS exome AF: 0.688

Gnomad FIN exome AF: 0.815

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.798

GnomAD4 exome AF: 0.788 AC: 1151042 AN: 1460454 Hom.: 454606 Cov.: 37 AF XY: 0.787 AC XY: 571879 AN XY: 726606

African (AFR) AF: 0.778 AC: 26004 AN: 33426

American (AMR) AF: 0.865 AC: 38647 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 21209 AN: 26118

East Asian (EAS) AF: 0.716 AC: 28414 AN: 39662

South Asian (SAS) AF: 0.752 AC: 64703 AN: 86074

European-Finnish (FIN) AF: 0.814 AC: 43459 AN: 53364

Middle Eastern (MID) AF: 0.806 AC: 4647 AN: 5766

European-Non Finnish (NFE) AF: 0.789 AC: 876691 AN: 1111048

Other (OTH) AF: 0.784 AC: 47268 AN: 60322

GnomAD4 genome AF: 0.792 AC: 120590 AN: 152210 Hom.: 47905 Cov.: 33 AF XY: 0.792 AC XY: 58948 AN XY: 74408

African (AFR) AF: 0.776 AC: 32217 AN: 41536

American (AMR) AF: 0.835 AC: 12764 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2832 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3669 AN: 5174

South Asian (SAS) AF: 0.743 AC: 3586 AN: 4828

European-Finnish (FIN) AF: 0.817 AC: 8645 AN: 10580

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54133 AN: 68010

Other (OTH) AF: 0.810 AC: 1713 AN: 2114

Alfa AF: 0.795 Hom.: 71217

Bravo AF: 0.791

Asia WGS AF: 0.738 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs2367707; hg19: chr4-75248434; COSMIC: COSV55261099; COSMIC: COSV55261099;