dbSNP rs2024125: HECW1:c.-32+4487G>A (chr7-43118878-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_015052.5(HECW1):c.-32+4487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,836 control chromosomes in the GnomAD database, including 22,675 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 0.54 ( 22674 hom., cov: 30)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

HECW1
NM_015052.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.311

Publications

11 publications found

Variant links:

Genes affected

HECW1 (HGNC:22195): (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including cellular protein metabolic process; negative regulation of sodium ion transmembrane transporter activity; and regulation of dendrite morphogenesis. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

HECW1 links:

HECW1-IT1 (HGNC:41465): (HECW1 intronic transcript 1)

HECW1-IT1 links:

ENSG00000310044 (HGNC:):

ENSG00000310044 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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015052.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HECW1	NM_015052.5	MANE Select	c.-32+4487G>A	intron	N/A	NP_055867.3	Q76N89-1
HECW1	NM_001287059.2		c.-32+5941G>A	intron	N/A	NP_001273988.1	Q76N89-2
HECW1-IT1	NR_135295.1		n.681-69G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HECW1	ENST00000395891.7	TSL:1 MANE Select	c.-32+4487G>A	intron	N/A	ENSP00000379228.1	Q76N89-1
HECW1	ENST00000857209.1		c.-32+5941G>A	intron	N/A	ENSP00000527268.1
HECW1	ENST00000453890.5	TSL:2	c.-32+5941G>A	intron	N/A	ENSP00000407774.1	Q76N89-2

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82152

AN:

151712

Hom.:

22663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.758

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.524

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.541

AC:

82198

AN:

151832

Hom.:

22674

Cov.:

AF XY:

0.550

AC XY:

40780

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.605

AC:

25024

AN:

41384

American (AMR)

AF:

0.525

AC:

8013

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1744

AN:

3462

East Asian (EAS)

AF:

0.758

AC:

3907

AN:

5152

South Asian (SAS)

AF:

0.540

AC:

2595

AN:

4810

European-Finnish (FIN)

AF:

0.636

AC:

6714

AN:

10560

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32526

AN:

67888

Other (OTH)

AF:

0.519

AC:

1093

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1876

3751

5627

7502

9378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.500

Hom.:

55121

Bravo

AF:

0.534

Asia WGS

AF:

0.598

AC:

2077

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.30

(source)

DANN

Benign

0.36

PhyloP100

-0.31

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over