rs7297415

Variant names:

• chr12-112223300-G-A
• rs7297415
• NM_001388303.1:c.6970+3343C>T

Variant summary

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

The NM_001388303.1(HECTD4):​c.6970+3343C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,156 control chromosomes in the GnomAD database, including 917 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 0.099 (917 hom., cov: 32)
• Consequence: HECTD4 NM_001388303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 12 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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388303.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD4	NM_001388303.1	MANE Select	c.6970+3343C>T		intron	N/A	NP_001375232.1
	HECTD4	NM_001109662.4		c.7000+3343C>T		intron	N/A	NP_001103132.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD4	ENST00000682272.1	MANE Select	c.6970+3343C>T		intron	N/A	ENSP00000507687.1
	HECTD4	ENST00000377560.9	TSL:5	c.6964+3343C>T		intron	N/A	ENSP00000366783.7
	HECTD4	ENST00000550722.5	TSL:5	c.6568+3343C>T		intron	N/A	ENSP00000449784.2

Frequencies

GnomAD3 genomes AF: 0.0993 AC: 15090 AN: 152038 Hom.: 916 Cov.: 32

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0952

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

GnomAD4 genome AF: 0.0993 AC: 15103 AN: 152156 Hom.: 917 Cov.: 32 AF XY: 0.104 AC XY: 7706 AN XY: 74398

African (AFR) AF: 0.0859 AC: 3565 AN: 41492

American (AMR) AF: 0.0980 AC: 1498 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3472

East Asian (EAS) AF: 0.0508 AC: 263 AN: 5176

South Asian (SAS) AF: 0.315 AC: 1521 AN: 4826

European-Finnish (FIN) AF: 0.0775 AC: 821 AN: 10594

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6905 AN: 67994

Other (OTH) AF: 0.0966 AC: 204 AN: 2112

Alfa AF: 0.102 Hom.: 1693

Bravo AF: 0.0928

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.6
DANN	Benign	0.89
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs7297415; hg19: chr12-112661104;