rs1460006

Variant names:

• chr4-74365527-C-G
• rs1460006
• NM_001432.3:c.67+152C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_001432.3(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 NM_001432.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 4 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]

ENSG00000304732 (HGNC:58817):

LOC105377276 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EREG	NM_001432.3	c.67+152C>G		intron_variant	Intron 1 of 4	ENST00000244869.3	NP_001423.1
LOC105377276	NR_188415.1	n.-186G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EREG	ENST00000244869.3	c.67+152C>G		intron_variant	Intron 1 of 4	1	NM_001432.3	ENSP00000244869.2
EREG	ENST00000507603.1	n.203+152C>G		intron_variant	Intron 1 of 2	2
ENSG00000304732	ENST00000805841.1	n.-186G>C		upstream_gene_variant

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

African (AFR) AF: 0.858 AC: 1054 AN: 1228

American (AMR) AF: 0.840 AC: 2077 AN: 2474

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 1422 AN: 1808

East Asian (EAS) AF: 0.699 AC: 1460 AN: 2088

South Asian (SAS) AF: 0.705 AC: 10776 AN: 15282

European-Finnish (FIN) AF: 0.789 AC: 3784 AN: 4796

Middle Eastern (MID) AF: 0.826 AC: 932 AN: 1128

European-Non Finnish (NFE) AF: 0.772 AC: 32234 AN: 41740

Other (OTH) AF: 0.768 AC: 2877 AN: 3744

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

African (AFR) AF: 0.879 AC: 33029 AN: 37578

American (AMR) AF: 0.866 AC: 12137 AN: 14016

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2813 AN: 3410

East Asian (EAS) AF: 0.728 AC: 3356 AN: 4610

South Asian (SAS) AF: 0.757 AC: 3188 AN: 4210

European-Finnish (FIN) AF: 0.828 AC: 7478 AN: 9034

Middle Eastern (MID) AF: 0.833 AC: 235 AN: 282

European-Non Finnish (NFE) AF: 0.814 AC: 53738 AN: 66050

Other (OTH) AF: 0.850 AC: 1629 AN: 1916

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
PhyloP100		-0.18
PromoterAI		0.15	Neutral
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: rs1460006; hg19: chr4-75231244;