Variant rs2274201 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

HECTD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.405 with no splicing effect.

BA1

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
HECTD1	NM_015382.4 linkuse as main transcript	c.360C>T	p.Ala120=	synonymous_variant	3/43	ENST00000399332.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECTD1	ENST00000399332.6 linkuse as main transcript	c.360C>T	p.Ala120=	synonymous_variant	3/43	5	NM_015382.4	P4

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76201

AN:

151738

Hom.:

20313

Cov.:

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.:

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

AF:

0.503

AC:

76316

AN:

151860

Hom.:

20360

Cov.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over