4-74382934-A-G

Position:

• chr4-74382934-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001432.3(EREG):​c.428+140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 630,632 control chromosomes in the GnomAD database, including 2,072 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 0.091 (1228 hom., cov: 33)
  • Exomes 𝑓: 0.039 (844 hom.)
• Consequence: EREG NM_001432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586

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]

EREG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EREG	NM_001432.3	c.428+140A>G		intron_variant		ENST00000244869.3	NP_001423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EREG	ENST00000244869.3	c.428+140A>G		intron_variant		1	NM_001432.3	ENSP00000244869.2
EREG	ENST00000503689.1	n.372+140A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13734 AN: 152152 Hom.: 1217 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.0991

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0783

GnomAD4 exome AF: 0.0389 AC: 18612 AN: 478362 Hom.: 844 AF XY: 0.0393 AC XY: 9840 AN XY: 250412

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.0578

Gnomad4 ASJ exome AF: 0.00933

Gnomad4 EAS exome AF: 0.0902

Gnomad4 SAS exome AF: 0.0820

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.0491

GnomAD4 genome AF: 0.0906 AC: 13792 AN: 152270 Hom.: 1228 Cov.: 33 AF XY: 0.0904 AC XY: 6731 AN XY: 74456

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0751

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.0992

Gnomad4 SAS AF: 0.0952

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0874

Alfa AF: 0.0615 Hom.: 86

Bravo AF: 0.0977

Asia WGS AF: 0.130 AC: 453 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.9
DANN	Benign	0.91

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: rs7675690; hg19: chr4-75248651;