rs7297415

Positions:

• chr12-112223300-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HECTD4	NM_001388303.1	c.6970+3343C>T		intron_variant		ENST00000682272.1	NP_001375232.1
HECTD4	NM_001109662.4	c.7000+3343C>T		intron_variant			NP_001103132.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HECTD4	ENST00000682272.1	c.6970+3343C>T		intron_variant			NM_001388303.1	ENSP00000507687.1
HECTD4	ENST00000377560.9	c.6964+3343C>T		intron_variant		5		ENSP00000366783.7
HECTD4	ENST00000550722.5	c.6568+3343C>T		intron_variant		5		ENSP00000449784.2
HECTD4	ENST00000550968.5	n.204+3343C>T		intron_variant		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

Gnomad4 AFR AF: 0.0859

Gnomad4 AMR AF: 0.0980

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.0508

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.0775

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0966

Alfa AF: 0.103 Hom.: 1268

Bravo AF: 0.0928

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.6
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs7297415; hg19: chr12-112661104;