rs11862356

Variant names:

• chr16-58476415-A-C
• rs11862356
• ENST00000394282.8:c.38-11341A>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.38-11341A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,222 control chromosomes in the GnomAD database, including 2,191 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 0.14 (2191 hom., cov: 33)
• Consequence: NDRG4 NM_001378332.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	NM_001378332.1		c.38-11341A>C		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.38-11341A>C		intron	N/A	NP_001365262.1
	NDRG4	NM_001378334.1		c.38-11341A>C		intron	N/A	NP_001365263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000394282.8	TSL:1	c.38-11341A>C		intron	N/A	ENSP00000377823.4
	NDRG4	ENST00000258187.9	TSL:1	c.-23-11341A>C		intron	N/A	ENSP00000258187.5
	NDRG4	ENST00000394279.6	TSL:5	c.-23-11341A>C		intron	N/A	ENSP00000377820.2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20709 AN: 152104 Hom.: 2184 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.136 AC: 20767 AN: 152222 Hom.: 2191 Cov.: 33 AF XY: 0.135 AC XY: 10072 AN XY: 74450

African (AFR) AF: 0.302 AC: 12513 AN: 41492

American (AMR) AF: 0.0823 AC: 1260 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.0605 AC: 313 AN: 5176

South Asian (SAS) AF: 0.0783 AC: 378 AN: 4828

European-Finnish (FIN) AF: 0.0784 AC: 832 AN: 10606

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0735 AC: 4997 AN: 68026

Other (OTH) AF: 0.108 AC: 228 AN: 2112

Alfa AF: 0.0974 Hom.: 874

Bravo AF: 0.143

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.56
PhyloP100		-0.42
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: rs11862356; hg19: chr16-58510319;