4-83427612-T-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_133636.5(HELQ):c.2627A>T(p.Tyr876Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,604,092 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.012 ( 29 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 26 hom. )
Consequence
HELQ
NM_133636.5 missense
NM_133636.5 missense
Scores
2
6
10
Clinical Significance
Conservation
PhyloP100: 8.00
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
?
Variant 4-83427612-T-A is Benign according to our data. Variant chr4-83427612-T-A is described in ClinVar as [Benign]. Clinvar id is 3038702.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1769/152302) while in subpopulation AFR AF= 0.0408 (1696/41566). AF 95% confidence interval is 0.0392. There are 29 homozygotes in gnomad4. There are 835 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 27 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HELQ | NM_133636.5 | c.2627A>T | p.Tyr876Phe | missense_variant | 13/18 | ENST00000295488.8 | |
HELQ | NM_001297755.2 | c.2426A>T | p.Tyr809Phe | missense_variant | 12/17 | ||
HELQ | NM_001297756.2 | c.1136A>T | p.Tyr379Phe | missense_variant | 13/18 | ||
HELQ | NM_001297757.2 | c.995A>T | p.Tyr332Phe | missense_variant | 12/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HELQ | ENST00000295488.8 | c.2627A>T | p.Tyr876Phe | missense_variant | 13/18 | 1 | NM_133636.5 | P1 | |
HELQ | ENST00000510985.1 | c.2426A>T | p.Tyr809Phe | missense_variant | 12/17 | 1 | |||
HELQ | ENST00000508591.5 | c.*1059A>T | 3_prime_UTR_variant, NMD_transcript_variant | 12/17 | 1 | ||||
HELQ | ENST00000512539.1 | n.115A>T | non_coding_transcript_exon_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0115 AC: 1753AN: 152184Hom.: 27 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1753
AN:
152184
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00295 AC: 713AN: 241480Hom.: 14 AF XY: 0.00192 AC XY: 251AN XY: 130856
GnomAD3 exomes
AF:
AC:
713
AN:
241480
Hom.:
AF XY:
AC XY:
251
AN XY:
130856
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00113 AC: 1636AN: 1451790Hom.: 26 Cov.: 29 AF XY: 0.000982 AC XY: 709AN XY: 722184
GnomAD4 exome
AF:
AC:
1636
AN:
1451790
Hom.:
Cov.:
29
AF XY:
AC XY:
709
AN XY:
722184
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0116 AC: 1769AN: 152302Hom.: 29 Cov.: 32 AF XY: 0.0112 AC XY: 835AN XY: 74488
GnomAD4 genome
?
AF:
AC:
1769
AN:
152302
Hom.:
Cov.:
32
AF XY:
AC XY:
835
AN XY:
74488
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
2
ESP6500AA
AF:
AC:
189
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
450
Asia WGS
AF:
AC:
11
AN:
3478
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 submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 15, 2019 | This 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -17
Find out detailed SpliceAI scores and Pangolin per-transcript scores at