rs2285808

chr12-112305969-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HECTD4	NM_001388303.1	c.1335+95G>A		intron_variant		ENST00000682272.1
HECTD4	NM_001109662.4	c.1335+95G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECTD4	ENST00000682272.1	c.1335+95G>A		intron_variant			NM_001388303.1	P4
HECTD4	ENST00000377560.9	c.1335+95G>A		intron_variant		5		A1
HECTD4	ENST00000550722.5	c.903+95G>A		intron_variant		5
HECTD4	ENST00000550724.2	c.319+13596G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8437 AN: 152150 Hom.: 1295 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0485

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.00496

Gnomad4 EAS exome AF: 0.633

Gnomad4 SAS exome AF: 0.0754

Gnomad4 FIN exome AF: 0.00334

Gnomad4 NFE exome AF: 0.00233

Gnomad4 OTH exome AF: 0.0468

GnomAD4 genome AF: 0.0554 AC: 8441 AN: 152268 Hom.: 1290 Cov.: 32 AF XY: 0.0620 AC XY: 4617 AN XY: 74454

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.0971

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0198 Hom.: 43

Bravo AF: 0.0706

Asia WGS AF: 0.243 AC: 843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	5.0
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs2285808; hg19: chr12-112743773; COSMIC: COSV66398285; COSMIC: COSV66398285;