16-58500126-A-G

Variant names:

• chr16-58500126-A-G
• rs79344693
• ENST00000566192.5:c.-123A>G

Variant summary

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

The ENST00000566192.5(NDRG4):​c.-123A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,533,340 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (31 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (24 hom.)
• Consequence: NDRG4 ENST00000566192.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40
• 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=-0.85).
• BP6: Variant 16-58500126-A-G is Benign according to our data. Variant chr16-58500126-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1317098.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1691/152290) while in subpopulation AFR AF = 0.0369 (1534/41548). AF 95% confidence interval is 0.0354. There are 31 homozygotes in GnomAd4. There are 769 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000566192.5. 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_001378332.1		c.178-862A>G		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.178-3618A>G		intron	N/A	NP_001365262.1
	NDRG4	NM_001378334.1		c.178-862A>G		intron	N/A	NP_001365263.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000566192.5	TSL:1	c.-123A>G		5_prime_UTR	Exon 1 of 14	ENSP00000454410.1	Q9ULP0-2
	NDRG4	ENST00000394282.8	TSL:1	c.178-3672A>G		intron	N/A	ENSP00000377823.4	Q9ULP0-6
	NDRG4	ENST00000258187.9	TSL:1	c.118-3672A>G		intron	N/A	ENSP00000258187.5	Q9ULP0-3

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1677 AN: 152172 Hom.: 30 Cov.: 33

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00815

GnomAD4 exome AF: 0.00139 AC: 1926 AN: 1381050 Hom.: 24 Cov.: 31 AF XY: 0.00127 AC XY: 867 AN XY: 681470

African (AFR) AF: 0.0379 AC: 1194 AN: 31530

American (AMR) AF: 0.00371 AC: 132 AN: 35554

Ashkenazi Jewish (ASJ) AF: 0.00160 AC: 40 AN: 25050

East Asian (EAS) AF: 0.00 AC: 0 AN: 35618

South Asian (SAS) AF: 0.0000890 AC: 7 AN: 78676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33690

Middle Eastern (MID) AF: 0.00319 AC: 18 AN: 5648

European-Non Finnish (NFE) AF: 0.000328 AC: 353 AN: 1077544

Other (OTH) AF: 0.00315 AC: 182 AN: 57740

GnomAD4 genome AF: 0.0111 AC: 1691 AN: 152290 Hom.: 31 Cov.: 33 AF XY: 0.0103 AC XY: 769 AN XY: 74480

African (AFR) AF: 0.0369 AC: 1534 AN: 41548

American (AMR) AF: 0.00627 AC: 96 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68012

Other (OTH) AF: 0.00806 AC: 17 AN: 2108

Alfa AF: 0.0226 Hom.: 13

Bravo AF: 0.0127

Asia WGS AF: 0.00173 AC: 6 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	-0.85
CADD	Benign	0.47
DANN	Benign	0.49
PhyloP100		-1.4
PromoterAI		0.17	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs79344693; hg19: chr16-58534030;