dbSNP rs2285808: HECTD4:c.1335+95G>A (chr12-112305969-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001388303.1(HECTD4):c.1335+95G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,147,894 control chromosomes in the GnomAD database, including 9,106 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.055 ( 1290 hom., cov: 32)

Exomes 𝑓: 0.036 ( 7816 hom. )

Consequence

HECTD4
NM_001388303.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.311

Publications

3 publications found

Variant links:

Genes affected

HECTD4 (HGNC:26611): (HECT domain E3 ubiquitin protein ligase 4) Predicted to enable ubiquitin-protein transferase activity. Involved in glucose homeostasis and glucose metabolic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

HECTD4 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Broad Center for Mendelian Genomics, G2P, Ambry Genetics, Baylor College of Medicine Research Center, Labcorp Genetics (formerly Invitae)

HECTD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388303.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD4	NM_001388303.1	MANE Select	c.1335+95G>A		intron	N/A	NP_001375232.1	A0A804HJX8
	HECTD4	NM_001109662.4		c.1335+95G>A		intron	N/A	NP_001103132.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HECTD4	ENST00000682272.1	MANE Select	c.1335+95G>A	intron	N/A	ENSP00000507687.1	A0A804HJX8
HECTD4	ENST00000377560.9	TSL:5	c.1335+95G>A	intron	N/A	ENSP00000366783.7	J3KPF0
HECTD4	ENST00000550722.5	TSL:5	c.903+95G>A	intron	N/A	ENSP00000449784.2	F8VWT9

Frequencies

GnomAD3 genomes

AF:

0.0555

AC:

8437

AN:

152150

Hom.:

1295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0534

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.0964

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.0636

GnomAD4 exome

AF:

0.0357

AC:

35509

AN:

995626

Hom.:

7816

AF XY:

0.0362

AC XY:

18103

AN XY:

500214

show subpopulations

African (AFR)

AF:

0.0485

AC:

1112

AN:

22934

American (AMR)

AF:

0.184

AC:

3946

AN:

21504

Ashkenazi Jewish (ASJ)

AF:

0.00496

AC:

AN:

17146

East Asian (EAS)

AF:

0.633

AC:

22061

AN:

34828

South Asian (SAS)

AF:

0.0754

AC:

4173

AN:

55318

European-Finnish (FIN)

AF:

0.00334

AC:

154

AN:

46116

Middle Eastern (MID)

AF:

0.0375

AC:

173

AN:

4616

European-Non Finnish (NFE)

AF:

0.00233

AC:

1748

AN:

749194

Other (OTH)

AF:

0.0468

AC:

2057

AN:

43970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

950

1900

2849

3799

4749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

384

768

1152

1536

1920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0554

AC:

8441

AN:

152268

Hom.:

1290

Cov.:

AF XY:

0.0620

AC XY:

4617

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0533

AC:

2214

AN:

41568

American (AMR)

AF:

0.144

AC:

2196

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.611

AC:

3156

AN:

5164

South Asian (SAS)

AF:

0.0971

AC:

468

AN:

4822

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00319

AC:

217

AN:

68022

Other (OTH)

AF:

0.0629

AC:

133

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

294

588

881

1175

1469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0198

Hom.:

Bravo

AF:

0.0706

Asia WGS

AF:

0.243

AC:

843

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

5.0

(source)

DANN

Benign

0.60

PhyloP100

-0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over