rs11066280

Variant names:

• chr12-112379979-T-A
• rs11066280
• NM_001388303.1:c.177+1973A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 91 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=-0.76).
• 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 rank	MANE	Protein	UniProt
HECTD4	NM_001388303.1	c.177+1973A>T		intron_variant	Intron 1 of 75	ENST00000682272.1	NP_001375232.1
HECTD4	NM_001109662.4	c.177+1973A>T		intron_variant	Intron 1 of 75		NP_001103132.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECTD4	ENST00000682272.1	c.177+1973A>T		intron_variant	Intron 1 of 75		NM_001388303.1	ENSP00000507687.1
HECTD4	ENST00000377560.9	c.177+1973A>T		intron_variant	Intron 1 of 75	5		ENSP00000366783.7
HECTD4	ENST00000550722.5	c.-256+1973A>T		intron_variant	Intron 1 of 75	5		ENSP00000449784.2
HECTD4	ENST00000550724.2	n.141+1973A>T		intron_variant	Intron 1 of 4	3		ENSP00000448061.2

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

African (AFR) AF: 0.00159 AC: 66 AN: 41496

American (AMR) AF: 0.000919 AC: 14 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.255 AC: 1316 AN: 5164

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4820

European-Finnish (FIN) AF: 0.0000965 AC: 1 AN: 10368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67952

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

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
PhyloP100		0.15
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: rs11066280; hg19: chr12-112817783;