chr12-112239475-A-G

Variant names:

• chr12-112239475-A-G
• rs11066209
• NM_001388303.1:c.5106-239T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.93).
• 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 rank	MANE	Protein	UniProt
HECTD4	NM_001388303.1	c.5106-239T>C		intron_variant	Intron 33 of 75	ENST00000682272.1	NP_001375232.1
HECTD4	NM_001109662.4	c.5136-239T>C		intron_variant	Intron 33 of 75		NP_001103132.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECTD4	ENST00000682272.1	c.5106-239T>C		intron_variant	Intron 33 of 75		NM_001388303.1	ENSP00000507687.1
HECTD4	ENST00000377560.9	c.5100-239T>C		intron_variant	Intron 33 of 75	5		ENSP00000366783.7
HECTD4	ENST00000550722.5	c.4704-239T>C		intron_variant	Intron 33 of 75	5		ENSP00000449784.2

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

African (AFR) AF: 0.0533 AC: 2218 AN: 41576

American (AMR) AF: 0.144 AC: 2201 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3466

East Asian (EAS) AF: 0.611 AC: 3161 AN: 5174

South Asian (SAS) AF: 0.0976 AC: 471 AN: 4828

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00319 AC: 217 AN: 68032

Other (OTH) AF: 0.0635 AC: 134 AN: 2110

Alfa AF: 0.0239 Hom.: 224

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
PhyloP100		-0.20
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: rs11066209; hg19: chr12-112677279;