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rs2274201

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_015382.4(HECTD1):​c.360C>T​(p.Ala120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,609,034 control chromosomes in the GnomAD database, including 154,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 20360 hom., cov: 31)
Exomes 𝑓: 0.42 ( 134311 hom. )

Consequence

HECTD1
NM_015382.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.405
Variant links:
Genes affected
HECTD1 (HGNC:20157): (HECT domain E3 ubiquitin protein ligase 1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in anatomical structure development; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and protein K63-linked ubiquitination. Predicted to act upstream of or within several processes, including animal organ development; negative regulation of protein localization to plasma membrane; and protein autoubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-31178035-G-A is Benign according to our data. Variant chr14-31178035-G-A is described in ClinVar as [Benign]. Clinvar id is 1178217.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=0.405 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 = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HECTD1NM_015382.4 linkuse as main transcriptc.360C>T p.Ala120= synonymous_variant 3/43 ENST00000399332.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HECTD1ENST00000399332.6 linkuse as main transcriptc.360C>T p.Ala120= synonymous_variant 3/435 NM_015382.4 P4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.502
AC:
76201
AN:
151738
Hom.:
20313
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.685
Gnomad AMI
AF:
0.314
Gnomad AMR
AF:
0.535
Gnomad ASJ
AF:
0.374
Gnomad EAS
AF:
0.441
Gnomad SAS
AF:
0.518
Gnomad FIN
AF:
0.413
Gnomad MID
AF:
0.401
Gnomad NFE
AF:
0.411
Gnomad OTH
AF:
0.485
GnomAD3 exomes
AF:
0.473
AC:
117830
AN:
249372
Hom.:
29141
AF XY:
0.462
AC XY:
62540
AN XY:
135304
show subpopulations
Gnomad AFR exome
AF:
0.685
Gnomad AMR exome
AF:
0.649
Gnomad ASJ exome
AF:
0.376
Gnomad EAS exome
AF:
0.432
Gnomad SAS exome
AF:
0.499
Gnomad FIN exome
AF:
0.418
Gnomad NFE exome
AF:
0.410
Gnomad OTH exome
AF:
0.441
GnomAD4 exome
AF:
0.423
AC:
616810
AN:
1457174
Hom.:
134311
Cov.:
33
AF XY:
0.424
AC XY:
307277
AN XY:
725204
show subpopulations
Gnomad4 AFR exome
AF:
0.694
Gnomad4 AMR exome
AF:
0.635
Gnomad4 ASJ exome
AF:
0.375
Gnomad4 EAS exome
AF:
0.431
Gnomad4 SAS exome
AF:
0.496
Gnomad4 FIN exome
AF:
0.426
Gnomad4 NFE exome
AF:
0.402
Gnomad4 OTH exome
AF:
0.429
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.503
AC:
76316
AN:
151860
Hom.:
20360
Cov.:
31
AF XY:
0.500
AC XY:
37116
AN XY:
74200
show subpopulations
Gnomad4 AFR
AF:
0.685
Gnomad4 AMR
AF:
0.536
Gnomad4 ASJ
AF:
0.374
Gnomad4 EAS
AF:
0.441
Gnomad4 SAS
AF:
0.518
Gnomad4 FIN
AF:
0.413
Gnomad4 NFE
AF:
0.411
Gnomad4 OTH
AF:
0.483
Alfa
AF:
0.432
Hom.:
24577
Bravo
AF:
0.519
Asia WGS
AF:
0.477
AC:
1658
AN:
3478
EpiCase
AF:
0.399
EpiControl
AF:
0.394

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 05, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
9.6
DANN
Benign
0.73
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

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

Other links and lift over

dbSNP: rs2274201; hg19: chr14-31647241; COSMIC: COSV67945562; COSMIC: COSV67945562; API