rs11066232

Variant names:

• chr12-112281362-C-T
• rs11066232
• NM_001388303.1:c.1528+1748G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388303.1(HECTD4):​c.1528+1748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 152,044 control chromosomes in the GnomAD database, including 1,289 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 0.056 (1289 hom., cov: 32)
• Consequence: HECTD4 NM_001388303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 2 publications found

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: Labcorp Genetics (formerly Invitae), Baylor College of Medicine Research Center, Broad Center for Mendelian Genomics, Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HECTD4	NM_001388303.1	c.1528+1748G>A		intron_variant	Intron 8 of 75	ENST00000682272.1	NP_001375232.1
HECTD4	NM_001109662.4	c.1528+1748G>A		intron_variant	Intron 8 of 75		NP_001103132.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECTD4	ENST00000682272.1	c.1528+1748G>A		intron_variant	Intron 8 of 75		NM_001388303.1	ENSP00000507687.1
HECTD4	ENST00000377560.9	c.1528+1748G>A		intron_variant	Intron 8 of 75	5		ENSP00000366783.7
HECTD4	ENST00000550722.5	c.1096+1748G>A		intron_variant	Intron 8 of 75	5		ENSP00000449784.2
HECTD4	ENST00000550724.2	n.320-11513G>A		intron_variant	Intron 2 of 4	3		ENSP00000448061.2

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8451 AN: 151924 Hom.: 1294 Cov.: 32

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.00218

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.0641

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0556 AC: 8456 AN: 152044 Hom.: 1289 Cov.: 32 AF XY: 0.0621 AC XY: 4611 AN XY: 74304

African (AFR) AF: 0.0542 AC: 2249 AN: 41486

American (AMR) AF: 0.143 AC: 2188 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.612 AC: 3147 AN: 5142

South Asian (SAS) AF: 0.0972 AC: 468 AN: 4816

European-Finnish (FIN) AF: 0.00218 AC: 23 AN: 10552

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00313 AC: 213 AN: 67990

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.0239 Hom.: 43

Bravo AF: 0.0708

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11066232; hg19: chr12-112719166;