16-58503518-G-A

Variant names:

• chr16-58503518-G-A
• rs79642910
• NM_001242835.2:c.22-280G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001242835.2(NDRG4):​c.22-280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0099 in 152,264 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0099 (28 hom., cov: 32)
• Consequence: NDRG4 NM_001242835.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.671
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-58503518-G-A is Benign according to our data. Variant chr16-58503518-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1317217.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0099 (1508/152264) while in subpopulation AFR AF = 0.0344 (1427/41538). AF 95% confidence interval is 0.0329. There are 28 homozygotes in GnomAd4. There are 712 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242835.2. 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_001242835.2	MANE Select	c.22-280G>A		intron	N/A	NP_001229764.1	A0A0S2Z5R7
	NDRG4	NM_001378332.1		c.268-280G>A		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.178-226G>A		intron	N/A	NP_001365262.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000570248.6	TSL:1 MANE Select	c.22-280G>A		intron	N/A	ENSP00000457659.1	Q9ULP0-1
	NDRG4	ENST00000394282.8	TSL:1	c.178-280G>A		intron	N/A	ENSP00000377823.4	Q9ULP0-6
	NDRG4	ENST00000258187.9	TSL:1	c.118-280G>A		intron	N/A	ENSP00000258187.5	Q9ULP0-3

Frequencies

GnomAD3 genomes AF: 0.00986 AC: 1500 AN: 152146 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00717

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

GnomAD4 genome AF: 0.00990 AC: 1508 AN: 152264 Hom.: 28 Cov.: 32 AF XY: 0.00957 AC XY: 712 AN XY: 74434

African (AFR) AF: 0.0344 AC: 1427 AN: 41538

American (AMR) AF: 0.00346 AC: 53 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68008

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.0177 Hom.: 15

Bravo AF: 0.0109

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.36
DANN	Benign	0.59
PhyloP100		-0.67
PromoterAI		-0.0036	Neutral
Mutation Taster		=100/0	polymorphism

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: rs79642910; hg19: chr16-58537422;