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GeneBe

4-83429687-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_133636.5(HELQ):c.2355G>A(p.Gln785=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000474 in 1,613,302 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 4 hom. )

Consequence

HELQ
NM_133636.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.98
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 Likely_benign. Variant got -5 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=-0.35).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-83429687-C-T is Benign according to our data. Variant chr4-83429687-C-T is described in ClinVar as [Benign]. Clinvar id is 3045631.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=1.98 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HELQNM_133636.5 linkuse as main transcriptc.2355G>A p.Gln785= synonymous_variant 12/18 ENST00000295488.8
HELQNM_001297755.2 linkuse as main transcriptc.2154G>A p.Gln718= synonymous_variant 11/17
HELQNM_001297756.2 linkuse as main transcriptc.864G>A p.Gln288= synonymous_variant 12/18
HELQNM_001297757.2 linkuse as main transcriptc.723G>A p.Gln241= synonymous_variant 11/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HELQENST00000295488.8 linkuse as main transcriptc.2355G>A p.Gln785= synonymous_variant 12/181 NM_133636.5 P1Q8TDG4-1
HELQENST00000510985.1 linkuse as main transcriptc.2154G>A p.Gln718= synonymous_variant 11/171
HELQENST00000508591.5 linkuse as main transcriptc.*787G>A 3_prime_UTR_variant, NMD_transcript_variant 11/171

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00285
AC:
434
AN:
152028
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00995
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000631
AC:
158
AN:
250508
Hom.:
1
AF XY:
0.000532
AC XY:
72
AN XY:
135430
show subpopulations
Gnomad AFR exome
AF:
0.00852
Gnomad AMR exome
AF:
0.000377
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000656
GnomAD4 exome
AF:
0.000225
AC:
329
AN:
1461156
Hom.:
4
Cov.:
30
AF XY:
0.000208
AC XY:
151
AN XY:
726882
show subpopulations
Gnomad4 AFR exome
AF:
0.00796
Gnomad4 AMR exome
AF:
0.000582
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00286
AC:
435
AN:
152146
Hom.:
1
Cov.:
32
AF XY:
0.00285
AC XY:
212
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00995
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00122
Hom.:
0
Bravo
AF:
0.00305

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 SciencesApr 09, 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
-0.35
Cadd
Benign
9.2
Dann
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs115975794; hg19: chr4-84350840; API