rs7687621

Variant names:

• chr4-74384109-T-C
• rs7687621
• NM_001432.3:c.429-618T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001432.3(EREG):​c.429-618T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,118 control chromosomes in the GnomAD database, including 50,564 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 0.81 (50564 hom., cov: 32)
• Consequence: EREG NM_001432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EREG	NM_001432.3	c.429-618T>C		intron_variant	Intron 4 of 4	ENST00000244869.3	NP_001423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EREG	ENST00000244869.3	c.429-618T>C		intron_variant	Intron 4 of 4	1	NM_001432.3	ENSP00000244869.2
EREG	ENST00000503689.1	n.373-618T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123724 AN: 151998 Hom.: 50514 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.819

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.814 AC: 123832 AN: 152118 Hom.: 50564 Cov.: 32 AF XY: 0.814 AC XY: 60505 AN XY: 74362

African (AFR) AF: 0.852 AC: 35392 AN: 41518

American (AMR) AF: 0.842 AC: 12887 AN: 15300

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

East Asian (EAS) AF: 0.710 AC: 3675 AN: 5178

South Asian (SAS) AF: 0.744 AC: 3583 AN: 4816

European-Finnish (FIN) AF: 0.815 AC: 8612 AN: 10562

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

European-Non Finnish (NFE) AF: 0.796 AC: 54087 AN: 67954

Other (OTH) AF: 0.821 AC: 1733 AN: 2112

Alfa AF: 0.805 Hom.: 70448

Bravo AF: 0.817

Asia WGS AF: 0.742 AC: 2576 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.74
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7687621; hg19: chr4-75249826;