dbSNP rs13385: HBEGF:c.*1006C>T (chr5-140333293-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001945.3(HBEGF):c.*1006C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 154,056 control chromosomes in the GnomAD database, including 3,323 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 0.19 ( 3253 hom., cov: 32)

Exomes 𝑓: 0.25 ( 70 hom. )

Consequence

HBEGF
NM_001945.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.795

Publications

29 publications found

Variant links:

Genes affected

HBEGF (HGNC:3059): (heparin binding EGF like growth factor) Enables growth factor activity and heparin binding activity. Involved in several processes, including epidermal growth factor receptor signaling pathway; positive regulation of protein kinase B signaling; and positive regulation of wound healing. Located in cell surface and extracellular space. Implicated in glomerulosclerosis and perinatal necrotizing enterocolitis. [provided by Alliance of Genome Resources, Apr 2022]

HBEGF links:

Genome browser will be placed here

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=-0.68).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBEGF	NM_001945.3 link	c.*1006C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000230990.7	NP_001936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBEGF	ENST00000230990.7 link	c.*1006C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001945.3	ENSP00000230990.6
HBEGF	ENST00000482211.2 link	n.*231C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28570

AN:

152094

Hom.:

3239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0660

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.251

AC:

462

AN:

1842

Hom.:

Cov.:

AF XY:

0.248

AC XY:

248

AN XY:

998

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.333

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

AN:

East Asian (EAS)

AF:

0.359

AC:

AN:

206

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.308

AC:

192

AN:

624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.196

AC:

166

AN:

848

Other (OTH)

AF:

0.145

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.188

AC:

28608

AN:

152214

Hom.:

3253

Cov.:

AF XY:

0.191

AC XY:

14181

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0662

AC:

2750

AN:

41564

American (AMR)

AF:

0.205

AC:

3132

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

525

AN:

3470

East Asian (EAS)

AF:

0.310

AC:

1605

AN:

5182

South Asian (SAS)

AF:

0.252

AC:

1214

AN:

4818

European-Finnish (FIN)

AF:

0.291

AC:

3074

AN:

10574

Middle Eastern (MID)

AF:

0.171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.231

AC:

15678

AN:

68000

Other (OTH)

AF:

0.188

AC:

398

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1158

2315

3473

4630

5788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.209

Hom.:

11369

Bravo

AF:

0.174

Asia WGS

AF:

0.288

AC:

1000

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.9

(source)

DANN

Benign

0.76

PhyloP100

0.80

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