rs11066209

Positions:

• chr12-112239475-A-G

Variant summary

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

The NM_001388303.1(HECTD4):​c.5106-239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,306 control chromosomes in the GnomAD database, including 1,296 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 (1296 hom., cov: 32)
• Consequence: HECTD4 NM_001388303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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=-0.93).
• 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.5106-239T>C		intron_variant		ENST00000682272.1
HECTD4	NM_001109662.4	c.5136-239T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HECTD4	ENST00000682272.1	c.5106-239T>C		intron_variant			NM_001388303.1	P4
HECTD4	ENST00000377560.9	c.5100-239T>C		intron_variant		5		A1
HECTD4	ENST00000550722.5	c.4704-239T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8455 AN: 152188 Hom.: 1301 Cov.: 32

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.0642

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

GnomAD4 genome AF: 0.0555 AC: 8459 AN: 152306 Hom.: 1296 Cov.: 32 AF XY: 0.0622 AC XY: 4632 AN XY: 74484

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.0635

Alfa AF: 0.0279 Hom.: 158

Bravo AF: 0.0706

Asia WGS AF: 0.241 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.80
DANN	Benign	0.28

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: rs11066209; hg19: chr12-112677279;