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GeneBe

4-83429717-A-G

Variant summary

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

The NM_133636.5(HELQ):c.2325T>C(p.His775=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,612,388 control chromosomes in the GnomAD database, including 3,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.090 ( 2058 hom., cov: 32)
Exomes 𝑓: 0.0093 ( 1836 hom. )

Consequence

HELQ
NM_133636.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0650
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=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-83429717-A-G is Benign according to our data. Variant chr4-83429717-A-G is described in ClinVar as [Benign]. Clinvar id is 3057036.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=0.065 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HELQNM_133636.5 linkuse as main transcriptc.2325T>C p.His775= synonymous_variant 12/18 ENST00000295488.8
HELQNM_001297755.2 linkuse as main transcriptc.2124T>C p.His708= synonymous_variant 11/17
HELQNM_001297756.2 linkuse as main transcriptc.834T>C p.His278= synonymous_variant 12/18
HELQNM_001297757.2 linkuse as main transcriptc.693T>C p.His231= synonymous_variant 11/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HELQENST00000295488.8 linkuse as main transcriptc.2325T>C p.His775= synonymous_variant 12/181 NM_133636.5 P1Q8TDG4-1
HELQENST00000510985.1 linkuse as main transcriptc.2124T>C p.His708= synonymous_variant 11/171
HELQENST00000508591.5 linkuse as main transcriptc.*757T>C 3_prime_UTR_variant, NMD_transcript_variant 11/171

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0895
AC:
13608
AN:
152092
Hom.:
2050
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.311
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0349
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000941
Gnomad OTH
AF:
0.0630
GnomAD3 exomes
AF:
0.0237
AC:
5911
AN:
249424
Hom.:
817
AF XY:
0.0171
AC XY:
2309
AN XY:
134792
show subpopulations
Gnomad AFR exome
AF:
0.319
Gnomad AMR exome
AF:
0.0155
Gnomad ASJ exome
AF:
0.00379
Gnomad EAS exome
AF:
0.000164
Gnomad SAS exome
AF:
0.000396
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.000941
Gnomad OTH exome
AF:
0.0103
GnomAD4 exome
AF:
0.00933
AC:
13628
AN:
1460178
Hom.:
1836
Cov.:
30
AF XY:
0.00819
AC XY:
5950
AN XY:
726380
show subpopulations
Gnomad4 AFR exome
AF:
0.322
Gnomad4 AMR exome
AF:
0.0180
Gnomad4 ASJ exome
AF:
0.00464
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.000582
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000490
Gnomad4 OTH exome
AF:
0.0211
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0897
AC:
13649
AN:
152210
Hom.:
2058
Cov.:
32
AF XY:
0.0863
AC XY:
6426
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.311
Gnomad4 AMR
AF:
0.0348
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000941
Gnomad4 OTH
AF:
0.0624
Alfa
AF:
0.0393
Hom.:
449
Bravo
AF:
0.102
Asia WGS
AF:
0.0300
AC:
106
AN:
3474

ClinVar

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

Submissions by phenotype

HELQ-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 14, 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
-0.64
Cadd
Benign
2.7
Dann
Benign
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs59255439; hg19: chr4-84350870; API