Genetic Variant HELQ:c.2190+125A>G (chr4-83432001-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_133636.5(HELQ):c.2190+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 559,070 control chromosomes in the GnomAD database, including 48,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.35 ( 11089 hom., cov: 32)

Exomes 𝑓: 0.42 ( 37052 hom. )

Consequence

HELQ
NM_133636.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.49

Publications

5 publications found

Variant links:

Genes affected

HELQ (HGNC:18536): (helicase, POLQ like) HEL308 is a single-stranded DNA-dependent ATPase and DNA helicase (Marini and Wood, 2002 [PubMed 11751861]).[supplied by OMIM, Mar 2008]

HELQ 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133636.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HELQ	NM_133636.5	MANE Select	c.2190+125A>G	intron	N/A	NP_598375.3	Q8TDG4-1
HELQ	NM_001297755.2		c.1989+125A>G	intron	N/A	NP_001284684.2	E3W980
HELQ	NM_001297756.2		c.699+125A>G	intron	N/A	NP_001284685.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HELQ	ENST00000295488.8	TSL:1 MANE Select	c.2190+125A>G	intron	N/A	ENSP00000295488.3	Q8TDG4-1
HELQ	ENST00000510985.1	TSL:1	c.1989+125A>G	intron	N/A	ENSP00000424539.1	E3W980
HELQ	ENST00000508591.5	TSL:1	n.*622+125A>G	intron	N/A	ENSP00000424186.1	E3W982

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52668

AN:

151768

Hom.:

11073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.328

GnomAD4 exome

AF:

0.416

AC:

169515

AN:

407184

Hom.:

37052

AF XY:

0.417

AC XY:

88698

AN XY:

212596

show subpopulations

African (AFR)

AF:

0.125

AC:

1179

AN:

9458

American (AMR)

AF:

0.513

AC:

5136

AN:

10020

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

3399

AN:

12222

East Asian (EAS)

AF:

0.631

AC:

15762

AN:

24972

South Asian (SAS)

AF:

0.450

AC:

8727

AN:

19412

European-Finnish (FIN)

AF:

0.464

AC:

13297

AN:

28672

Middle Eastern (MID)

AF:

0.273

AC:

493

AN:

1804

European-Non Finnish (NFE)

AF:

0.405

AC:

112557

AN:

277790

Other (OTH)

AF:

0.393

AC:

8965

AN:

22834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4909

9818

14726

19635

24544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1556

3112

4668

6224

7780

<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:

0.347

AC:

52704

AN:

151886

Hom.:

11089

Cov.:

AF XY:

0.357

AC XY:

26479

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.127

AC:

5258

AN:

41502

American (AMR)

AF:

0.464

AC:

7082

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

984

AN:

3470

East Asian (EAS)

AF:

0.673

AC:

3482

AN:

5172

South Asian (SAS)

AF:

0.486

AC:

2342

AN:

4818

European-Finnish (FIN)

AF:

0.456

AC:

4768

AN:

10450

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27669

AN:

67916

Other (OTH)

AF:

0.333

AC:

703

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1614

3228

4843

6457

8071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.252

Hom.:

726

Bravo

AF:

0.336

Asia WGS

AF:

0.574

AC:

1975

AN:

3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.21

(source)

DANN

Benign

0.82

PhyloP100

-2.5

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