rs11066188

Variant names:

• chr12-112172910-G-A
• rs11066188
• NM_001388303.1:c.11595-49C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-112172910-G-A
• chr12-112172910-G-C
• chr12-112172910-G-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.11595-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,503,978 control chromosomes in the GnomAD database, including 111,020 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 0.28 (8493 hom., cov: 32)
  • Exomes 𝑓: 0.37 (102527 hom.)
• Consequence: HECTD4 NM_001388303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 61 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: Broad Center for Mendelian Genomics, G2P, Ambry Genetics, Baylor College of Medicine Research Center, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD4	NM_001388303.1	MANE Select	c.11595-49C>T		intron	N/A	NP_001375232.1	A0A804HJX8
	HECTD4	NM_001109662.4		c.11625-49C>T		intron	N/A	NP_001103132.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD4	ENST00000682272.1	MANE Select	c.11595-49C>T		intron	N/A	ENSP00000507687.1	A0A804HJX8
	HECTD4	ENST00000377560.9	TSL:5	c.11589-49C>T		intron	N/A	ENSP00000366783.7	J3KPF0
	HECTD4	ENST00000550722.5	TSL:5	c.11193-49C>T		intron	N/A	ENSP00000449784.2	F8VWT9

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43123 AN: 151954 Hom.: 8498 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.300 AC: 73161 AN: 243690 AF XY: 0.302

Gnomad AFR exome AF: 0.0576

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.635

Gnomad EAS exome AF: 0.000502

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.368 AC: 497731 AN: 1351906 Hom.: 102527 Cov.: 20 AF XY: 0.363 AC XY: 245219 AN XY: 676114

African (AFR) AF: 0.0566 AC: 1773 AN: 31318

American (AMR) AF: 0.207 AC: 9184 AN: 44376

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 15902 AN: 25214

East Asian (EAS) AF: 0.000487 AC: 19 AN: 39038

South Asian (SAS) AF: 0.0916 AC: 7657 AN: 83634

European-Finnish (FIN) AF: 0.378 AC: 19617 AN: 51886

Middle Eastern (MID) AF: 0.321 AC: 1714 AN: 5344

European-Non Finnish (NFE) AF: 0.416 AC: 421884 AN: 1014512

Other (OTH) AF: 0.353 AC: 19981 AN: 56584

GnomAD4 genome AF: 0.283 AC: 43101 AN: 152072 Hom.: 8493 Cov.: 32 AF XY: 0.275 AC XY: 20444 AN XY: 74346

African (AFR) AF: 0.0696 AC: 2887 AN: 41504

American (AMR) AF: 0.258 AC: 3940 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2260 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.0774 AC: 373 AN: 4820

European-Finnish (FIN) AF: 0.376 AC: 3987 AN: 10590

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28524 AN: 67944

Other (OTH) AF: 0.311 AC: 655 AN: 2104

Alfa AF: 0.366 Hom.: 11972

Bravo AF: 0.270

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-1.1
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: rs11066188; hg19: chr12-112610714; COSMIC: COSV66391499; COSMIC: COSV66391499;