rs11066280

Positions:

• chr12-112379979-T-A
• chr12-112379979-T-G

Variant summary

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

The NM_001388303.1(HECTD4):​c.177+1973A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 151,826 control chromosomes in the GnomAD database, including 171 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 0.0095 (171 hom., cov: 32)
• Consequence: HECTD4 NM_001388303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HECTD4	NM_001388303.1	c.177+1973A>T		intron_variant		ENST00000682272.1	NP_001375232.1
HECTD4	NM_001109662.4	c.177+1973A>T		intron_variant			NP_001103132.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HECTD4	ENST00000682272.1	c.177+1973A>T		intron_variant			NM_001388303.1	ENSP00000507687	P4
HECTD4	ENST00000377560.9	c.177+1973A>T		intron_variant		5		ENSP00000366783	A1
HECTD4	ENST00000550722.5	c.-256+1973A>T		intron_variant		5		ENSP00000449784
HECTD4	ENST00000550724.2	c.141+1973A>T		intron_variant, NMD_transcript_variant		3		ENSP00000448061

Frequencies

GnomAD3 genomes AF: 0.00951 AC: 1443 AN: 151710 Hom.: 171 Cov.: 32

Gnomad AFR AF: 0.00160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000920

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0000965

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00527

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

GnomAD4 genome AF: 0.00947 AC: 1438 AN: 151826 Hom.: 171 Cov.: 32 AF XY: 0.0111 AC XY: 820 AN XY: 74192

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.000919

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.0000965

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00822 Hom.: 68

Bravo AF: 0.0104

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.53

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: rs11066280; hg19: chr12-112817783; COSMIC: COSV66387333;