rs1460006

Positions:

• chr4-74365527-C-G
• chr4-74365527-C-T

Variant summary

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

The ENST00000244869.3(EREG):​c.67+152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 216,278 control chromosomes in the GnomAD database, including 70,907 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 0.83 (49341 hom., cov: 17)
  • Exomes 𝑓: 0.76 (21566 hom.)
• Consequence: EREG ENST00000244869.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EREG	NM_001432.3	c.67+152C>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.67+152C>G		intron_variant		1	NM_001432.3	ENSP00000244869	P1
EREG	ENST00000507603.1	n.203+152C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.834 AC: 118287 AN: 141880 Hom.: 49287 Cov.: 17

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.848

GnomAD4 exome AF: 0.762 AC: 56616 AN: 74288 Hom.: 21566 AF XY: 0.755 AC XY: 31289 AN XY: 41458

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 0.699

Gnomad4 SAS exome AF: 0.705

Gnomad4 FIN exome AF: 0.789

Gnomad4 NFE exome AF: 0.772

Gnomad4 OTH exome AF: 0.768

GnomAD4 genome AF: 0.834 AC: 118395 AN: 141990 Hom.: 49341 Cov.: 17 AF XY: 0.835 AC XY: 57272 AN XY: 68614

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.850

Alfa AF: 0.773 Hom.: 2350

Bravo AF: 0.835

Asia WGS AF: 0.743 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.50

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: rs1460006; hg19: chr4-75231244;