dbSNP rs7675690: EREG:c.428+140A>G (chr4-74382934-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.586

Publications

3 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EREG	NM_001432.3 link	c.428+140A>G		intron_variant	Intron 4 of 4	ENST00000244869.3	NP_001423.1	O14944

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EREG	ENST00000244869.3 link	c.428+140A>G		intron_variant	Intron 4 of 4	1	NM_001432.3	ENSP00000244869.2		O14944
EREG	ENST00000503689.1 link	n.372+140A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0903

AC:

13734

AN:

152152

Hom.:

1217

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.224

AC:

2958

AN:

13234

American (AMR)

AF:

0.0578

AC:

1176

AN:

20336

Ashkenazi Jewish (ASJ)

AF:

0.00933

AC:

122

AN:

13072

East Asian (EAS)

AF:

0.0902

AC:

2938

AN:

32578

South Asian (SAS)

AF:

0.0820

AC:

2718

AN:

33128

European-Finnish (FIN)

AF:

0.0320

AC:

956

AN:

29844

Middle Eastern (MID)

AF:

0.0278

AC:

AN:

1944

European-Non Finnish (NFE)

AF:

0.0208

AC:

6401

AN:

307998

Other (OTH)

AF:

0.0491

AC:

1289

AN:

26228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

783

1567

2350

3134

3917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0906

AC:

13792

AN:

152270

Hom.:

1228

Cov.:

AF XY:

0.0904

AC XY:

6731

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.229

AC:

9516

AN:

41526

American (AMR)

AF:

0.0751

AC:

1149

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.0992

AC:

514

AN:

5184

South Asian (SAS)

AF:

0.0952

AC:

460

AN:

4832

European-Finnish (FIN)

AF:

0.0303

AC:

322

AN:

10624

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0235

AC:

1598

AN:

68014

Other (OTH)

AF:

0.0874

AC:

185

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

565

1130

1694

2259

2824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0670

Hom.:

103

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

(source)

DANN

Benign

0.91

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over