rs10518126

chr4-74377402-C-T

Variant summary

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

The NM_001432.3(EREG):c.68-2046C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 152,086 control chromosomes in the GnomAD database, including 749 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 0.075 (749 hom., cov: 32)
• Consequence: EREG NM_001432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EREG	NM_001432.3	c.68-2046C>T		intron_variant		ENST00000244869.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EREG	ENST00000244869.3	c.68-2046C>T		intron_variant		1	NM_001432.3	P1
EREG	ENST00000507603.1	n.204-2046C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11368 AN: 151968 Hom.: 732 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.0977

Gnomad FIN AF: 0.0305

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0752 AC: 11434 AN: 152086 Hom.: 749 Cov.: 32 AF XY: 0.0757 AC XY: 5625 AN XY: 74344

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0721

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.0998

Gnomad4 SAS AF: 0.0984

Gnomad4 FIN AF: 0.0305

Gnomad4 NFE AF: 0.0234

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0296 Hom.: 215

Bravo AF: 0.0800

Asia WGS AF: 0.135 AC: 469 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.6
Dann	Benign	0.19

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: rs10518126; hg19: chr4-75243119;