rs2367707

Positions:

• chr4-74382717-A-G
• chr4-74382717-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001432.3(EREG):​c.351A>G​(p.Glu117=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EREG	NM_001432.3	c.351A>G	p.Glu117=	synonymous_variant	4/5	ENST00000244869.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EREG	ENST00000244869.3	c.351A>G	p.Glu117=	synonymous_variant	4/5	1	NM_001432.3	P1
EREG	ENST00000503689.1	n.295A>G		non_coding_transcript_exon_variant	1/2	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

GnomAD3 exomes AF: 0.794 AC: 199453 AN: 251048 Hom.: 79711 AF XY: 0.790 AC XY: 107152 AN XY: 135708

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 SAS exome AF: 0.750

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

Gnomad4 AFR exome AF: 0.778

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.812

Gnomad4 EAS exome AF: 0.716

Gnomad4 SAS exome AF: 0.752

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.789

Gnomad4 OTH exome AF: 0.784

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

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.810

Alfa AF: 0.795 Hom.: 61118

Bravo AF: 0.791

Asia WGS AF: 0.738 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs2367707; hg19: chr4-75248434; COSMIC: COSV55261099; COSMIC: COSV55261099;