dbSNP rs2074613: HBEGF:c.555-231G>A (chr5-140334979-C-T) – 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.555-231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 583,366 control chromosomes in the GnomAD database, including 91,959 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 0.60 ( 27672 hom., cov: 32)

Exomes 𝑓: 0.54 ( 64287 hom. )

Consequence

HBEGF
NM_001945.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

11 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

new If you want to explore the variant's impact on the transcript NM_001945.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 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.555-231G>A		intron	N/A	NP_001936.1	Q99075

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HBEGF	ENST00000230990.7	TSL:1 MANE Select	c.555-231G>A	intron	N/A	ENSP00000230990.6	Q99075
HBEGF	ENST00000950444.1		c.555-231G>A	intron	N/A	ENSP00000620503.1
HBEGF	ENST00000950442.1		c.555-240G>A	intron	N/A	ENSP00000620501.1

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90544

AN:

151906

Hom.:

27653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.736

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.506

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.586

GnomAD4 exome

AF:

0.543

AC:

234327

AN:

431340

Hom.:

64287

Cov.:

AF XY:

0.541

AC XY:

123096

AN XY:

227538

show subpopulations

African (AFR)

AF:

0.732

AC:

8817

AN:

12038

American (AMR)

AF:

0.548

AC:

9845

AN:

17974

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

6360

AN:

13112

East Asian (EAS)

AF:

0.506

AC:

15152

AN:

29974

South Asian (SAS)

AF:

0.492

AC:

21969

AN:

44636

European-Finnish (FIN)

AF:

0.508

AC:

14858

AN:

29224

Middle Eastern (MID)

AF:

0.539

AC:

1013

AN:

1878

European-Non Finnish (NFE)

AF:

0.553

AC:

142464

AN:

257572

Other (OTH)

AF:

0.555

AC:

13849

AN:

24932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

4837

9674

14510

19347

24184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.596

AC:

90598

AN:

152026

Hom.:

27672

Cov.:

AF XY:

0.591

AC XY:

43956

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.736

AC:

30521

AN:

41482

American (AMR)

AF:

0.563

AC:

8593

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1686

AN:

3470

East Asian (EAS)

AF:

0.545

AC:

2815

AN:

5162

South Asian (SAS)

AF:

0.477

AC:

2299

AN:

4816

European-Finnish (FIN)

AF:

0.506

AC:

5343

AN:

10554

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.552

AC:

37496

AN:

67948

Other (OTH)

AF:

0.582

AC:

1230

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1731

3462

5192

6923

8654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.569

Hom.:

8893

Bravo

AF:

0.610

Asia WGS

AF:

0.496

AC:

1725

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.75

PhyloP100

-1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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