rs11862356

chr16-58476415-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000394282.8(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 ENST00000394282.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001130487.2	c.38-11341A>C		intron_variant
NDRG4	NM_001363869.2	c.-376-11341A>C		intron_variant
NDRG4	NM_001378332.1	c.38-11341A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000258187.9	c.-23-11341A>C		intron_variant		1
NDRG4	ENST00000394282.8	c.38-11341A>C		intron_variant		1
NDRG4	ENST00000394279.6	c.-23-11341A>C		intron_variant		5

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

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.0823

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.0605

Gnomad4 SAS AF: 0.0783

Gnomad4 FIN AF: 0.0784

Gnomad4 NFE AF: 0.0735

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0946 Hom.: 596

Bravo AF: 0.143

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.28
Dann	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11862356; hg19: chr16-58510319;