16-58503993-G-A

Variant names:

• chr16-58503993-G-A
• rs2427787
• NM_001242835.2:c.127+90G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001242835.2(NDRG4):​c.127+90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,528,942 control chromosomes in the GnomAD database, including 150,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11370 hom., cov: 31)
  • Exomes 𝑓: 0.44 (139175 hom.)
• Consequence: NDRG4 NM_001242835.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.86
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-58503993-G-A is Benign according to our data. Variant chr16-58503993-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

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.127+90G>A		intron	N/A	NP_001229764.1	A0A0S2Z5R7
	NDRG4	NM_001378332.1		c.373+90G>A		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.337+90G>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.127+90G>A		intron	N/A	ENSP00000457659.1	Q9ULP0-1
	NDRG4	ENST00000394282.8	TSL:1	c.283+90G>A		intron	N/A	ENSP00000377823.4	Q9ULP0-6
	NDRG4	ENST00000258187.9	TSL:1	c.223+90G>A		intron	N/A	ENSP00000258187.5	Q9ULP0-3

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54557 AN: 151550 Hom.: 11365 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.389 AC: 93137 AN: 239488 AF XY: 0.400

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.229

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.469

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.441 AC: 607601 AN: 1377272 Hom.: 139175 Cov.: 24 AF XY: 0.441 AC XY: 303858 AN XY: 688898

African (AFR) AF: 0.148 AC: 4762 AN: 32200

American (AMR) AF: 0.264 AC: 11768 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 11616 AN: 25532

East Asian (EAS) AF: 0.224 AC: 8798 AN: 39328

South Asian (SAS) AF: 0.404 AC: 34252 AN: 84690

European-Finnish (FIN) AF: 0.464 AC: 20761 AN: 44778

Middle Eastern (MID) AF: 0.388 AC: 1951 AN: 5034

European-Non Finnish (NFE) AF: 0.469 AC: 489202 AN: 1043500

Other (OTH) AF: 0.424 AC: 24491 AN: 57716

GnomAD4 genome AF: 0.360 AC: 54576 AN: 151670 Hom.: 11370 Cov.: 31 AF XY: 0.358 AC XY: 26517 AN XY: 74074

African (AFR) AF: 0.158 AC: 6552 AN: 41438

American (AMR) AF: 0.325 AC: 4965 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1181 AN: 5098

South Asian (SAS) AF: 0.399 AC: 1917 AN: 4806

European-Finnish (FIN) AF: 0.488 AC: 5111 AN: 10484

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.473 AC: 32041 AN: 67806

Other (OTH) AF: 0.374 AC: 789 AN: 2112

Alfa AF: 0.361 Hom.: 4099

Bravo AF: 0.335

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.012
DANN	Benign	0.38
PhyloP100		-1.9
PromoterAI		0.0036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2427787; hg19: chr16-58537897; COSMIC: COSV50748712; COSMIC: COSV50748712;