rs7687621

Positions:

• chr4-74384109-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
EREG	NM_001432.3	c.429-618T>C		intron_variant		ENST00000244869.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EREG	ENST00000244869.3	c.429-618T>C		intron_variant		1	NM_001432.3	P1
EREG	ENST00000503689.1	n.373-618T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.821

Alfa AF: 0.812 Hom.: 6611

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7687621; hg19: chr4-75249826;