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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001945.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBEGF	NM_001945.3	MANE Select	c.*1006C>T		3_prime_UTR	Exon 6 of 6	NP_001936.1	Q99075

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HBEGF	ENST00000230990.7	TSL:1 MANE Select	c.*1006C>T	3_prime_UTR	Exon 6 of 6	ENSP00000230990.6	Q99075
HBEGF	ENST00000950442.1		c.*1006C>T	3_prime_UTR	Exon 6 of 6	ENSP00000620501.1
HBEGF	ENST00000950443.1		c.*1006C>T	3_prime_UTR	Exon 5 of 5	ENSP00000620502.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over