rs11076243

Variant names:

• chr16-58475247-A-C
• rs11076243
• ENST00000394282.8:c.37+10780A>C

Variant summary

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

The NM_001378332.1(NDRG4):​c.37+10780A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,300 control chromosomes in the GnomAD database, including 183 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 0.046 (183 hom., cov: 32)
• Consequence: NDRG4 NM_001378332.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.872
• Publications: 6 publications found

Genes affected

NDRG4 (HGNC:14466): (NDRG family member 4) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that is required for cell cycle progression and survival in primary astrocytes and may be involved in the regulation of mitogenic signalling in vascular smooth muscles cells. Alternative splicing results in multiple transcripts encoding different isoforms.[provided by RefSeq, Jun 2011]

NDRG4 Gene-Disease associations (from GenCC):

• achromatopsia

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378332.1. 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
	NDRG4	NM_001378332.1		c.37+10780A>C		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.37+10780A>C		intron	N/A	NP_001365262.1
	NDRG4	NM_001378334.1		c.37+10780A>C		intron	N/A	NP_001365263.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000394282.8	TSL:1	c.37+10780A>C		intron	N/A	ENSP00000377823.4
	NDRG4	ENST00000258187.9	TSL:1	c.-24+11450A>C		intron	N/A	ENSP00000258187.5
	NDRG4	ENST00000394279.6	TSL:5	c.-24+10176A>C		intron	N/A	ENSP00000377820.2

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6982 AN: 152182 Hom.: 183 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0295

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0377

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

GnomAD4 genome AF: 0.0459 AC: 6991 AN: 152300 Hom.: 183 Cov.: 32 AF XY: 0.0455 AC XY: 3388 AN XY: 74464

African (AFR) AF: 0.0623 AC: 2589 AN: 41556

American (AMR) AF: 0.0294 AC: 450 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5186

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4830

European-Finnish (FIN) AF: 0.0545 AC: 579 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3065 AN: 68020

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0443 Hom.: 257

Bravo AF: 0.0447

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.6
DANN	Benign	0.72
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11076243; hg19: chr16-58509151;