rs40186

Variant names:

• chr16-58511164-G-A
• rs40186
• NM_001242835.2:c.905-258G>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.905-258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 515,904 control chromosomes in the GnomAD database, including 6,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1647 hom., cov: 33)
  • Exomes 𝑓: 0.15 (4764 hom.)
• Consequence: NDRG4 NM_001242835.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.34
• 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=-0.92).
• BP6: Variant 16-58511164-G-A is Benign according to our data. Variant chr16-58511164-G-A is described in ClinVar as Benign. ClinVar VariationId is 1228881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 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.905-258G>A		intron	N/A	NP_001229764.1	A0A0S2Z5R7
	NDRG4	NM_001378332.1		c.1151-258G>A		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.1115-258G>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.905-258G>A		intron	N/A	ENSP00000457659.1	Q9ULP0-1
	NDRG4	ENST00000394282.8	TSL:1	c.1022-258G>A		intron	N/A	ENSP00000377823.4	Q9ULP0-6
	NDRG4	ENST00000258187.9	TSL:1	c.962-258G>A		intron	N/A	ENSP00000258187.5	Q9ULP0-3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19784 AN: 152076 Hom.: 1643 Cov.: 33

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.154 AC: 55831 AN: 363710 Hom.: 4764 Cov.: 2 AF XY: 0.152 AC XY: 28634 AN XY: 188980

African (AFR) AF: 0.0365 AC: 402 AN: 11020

American (AMR) AF: 0.252 AC: 3408 AN: 13538

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 1953 AN: 11692

East Asian (EAS) AF: 0.170 AC: 4492 AN: 26360

South Asian (SAS) AF: 0.111 AC: 3390 AN: 30404

European-Finnish (FIN) AF: 0.160 AC: 4023 AN: 25210

Middle Eastern (MID) AF: 0.127 AC: 212 AN: 1668

European-Non Finnish (NFE) AF: 0.156 AC: 34626 AN: 221926

Other (OTH) AF: 0.152 AC: 3325 AN: 21892

GnomAD4 genome AF: 0.130 AC: 19813 AN: 152194 Hom.: 1647 Cov.: 33 AF XY: 0.131 AC XY: 9773 AN XY: 74388

African (AFR) AF: 0.0362 AC: 1503 AN: 41536

American (AMR) AF: 0.238 AC: 3633 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.183 AC: 945 AN: 5154

South Asian (SAS) AF: 0.117 AC: 563 AN: 4828

European-Finnish (FIN) AF: 0.152 AC: 1609 AN: 10604

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.155 AC: 10532 AN: 67986

Other (OTH) AF: 0.135 AC: 285 AN: 2116

Alfa AF: 0.148 Hom.: 4372

Bravo AF: 0.133

Asia WGS AF: 0.152 AC: 532 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	-0.92
CADD	Benign	0.16
DANN	Benign	0.79
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs40186; hg19: chr16-58545068;