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rs7665103

chr4-83443598-A-Gchr4-83443598-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_133636.5(HELQ):c.1482T>C(p.Ile494=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,524,536 control chromosomes in the GnomAD database, including 137,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.44 ( 15189 hom., cov: 32)
Exomes 𝑓: 0.41 ( 122226 hom. )

Consequence

HELQ
NM_133636.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-83443598-A-G is Benign according to our data. Variant chr4-83443598-A-G is described in ClinVar as [Benign]. Clinvar id is 3059382.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.66 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HELQNM_133636.5 linkuse as main transcriptc.1482T>C p.Ile494= synonymous_variant 6/18 ENST00000295488.8
HELQNM_001297755.2 linkuse as main transcriptc.1281T>C p.Ile427= synonymous_variant 5/17
HELQNM_001297756.2 linkuse as main transcriptc.-23T>C 5_prime_UTR_variant 6/18
HELQNM_001297757.2 linkuse as main transcriptc.-69-2195T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HELQENST00000295488.8 linkuse as main transcriptc.1482T>C p.Ile494= synonymous_variant 6/181 NM_133636.5 P1Q8TDG4-1
HELQENST00000510985.1 linkuse as main transcriptc.1281T>C p.Ile427= synonymous_variant 5/171
HELQENST00000508591.5 linkuse as main transcriptc.1466-2195T>C intron_variant, NMD_transcript_variant 1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.439
AC:
66697
AN:
151872
Hom.:
15163
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.446
Gnomad AMI
AF:
0.372
Gnomad AMR
AF:
0.501
Gnomad ASJ
AF:
0.276
Gnomad EAS
AF:
0.666
Gnomad SAS
AF:
0.496
Gnomad FIN
AF:
0.454
Gnomad MID
AF:
0.277
Gnomad NFE
AF:
0.409
Gnomad OTH
AF:
0.394
GnomAD3 exomes
AF:
0.456
AC:
106435
AN:
233522
Hom.:
25526
AF XY:
0.446
AC XY:
56359
AN XY:
126258
show subpopulations
Gnomad AFR exome
AF:
0.439
Gnomad AMR exome
AF:
0.607
Gnomad ASJ exome
AF:
0.263
Gnomad EAS exome
AF:
0.662
Gnomad SAS exome
AF:
0.463
Gnomad FIN exome
AF:
0.462
Gnomad NFE exome
AF:
0.399
Gnomad OTH exome
AF:
0.414
GnomAD4 exome
AF:
0.415
AC:
569357
AN:
1372546
Hom.:
122226
Cov.:
21
AF XY:
0.415
AC XY:
284714
AN XY:
685400
show subpopulations
Gnomad4 AFR exome
AF:
0.437
Gnomad4 AMR exome
AF:
0.591
Gnomad4 ASJ exome
AF:
0.262
Gnomad4 EAS exome
AF:
0.639
Gnomad4 SAS exome
AF:
0.462
Gnomad4 FIN exome
AF:
0.464
Gnomad4 NFE exome
AF:
0.397
Gnomad4 OTH exome
AF:
0.417
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.439
AC:
66775
AN:
151990
Hom.:
15189
Cov.:
32
AF XY:
0.446
AC XY:
33096
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.446
Gnomad4 AMR
AF:
0.502
Gnomad4 ASJ
AF:
0.276
Gnomad4 EAS
AF:
0.666
Gnomad4 SAS
AF:
0.496
Gnomad4 FIN
AF:
0.454
Gnomad4 NFE
AF:
0.409
Gnomad4 OTH
AF:
0.399
Alfa
AF:
0.402
Hom.:
16294
Bravo
AF:
0.440
Asia WGS
AF:
0.603
AC:
2096
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

HELQ-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
6.9
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7665103; hg19: chr4-84364751; COSMIC: COSV55028346; API