chr16-58464080-G-T

Variant names:

• chr16-58464080-G-T
• rs111484016
• ENST00000394282.8:c.-351G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000394282.8(NDRG4):​c.-351G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 244,438 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (103 hom., cov: 32)
  • Exomes 𝑓: 0.022 (35 hom.)
• Consequence: NDRG4 ENST00000394282.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02
• 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

ENSG00000294769 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-58464080-G-T is Benign according to our data. Variant chr16-58464080-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1316103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0297 (4514/152090) while in subpopulation AFR AF = 0.0483 (2008/41536). AF 95% confidence interval is 0.0466. There are 103 homozygotes in GnomAd4. There are 2160 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 103 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394282.8. 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_001378338.1		c.-24+283G>T		intron	N/A	NP_001365267.1
	NDRG4	NM_001378339.1		c.-24+283G>T		intron	N/A	NP_001365268.1
	NDRG4	NM_001378342.1		c.-24+283G>T		intron	N/A	NP_001365271.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000394282.8	TSL:1	c.-351G>T		5_prime_UTR	Exon 1 of 16	ENSP00000377823.4	Q9ULP0-6
	NDRG4	ENST00000258187.9	TSL:1	c.-24+283G>T		intron	N/A	ENSP00000258187.5	Q9ULP0-3
	NDRG4	ENST00000889964.1		c.-165+283G>T		intron	N/A	ENSP00000560023.1

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4502 AN: 151984 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0254

GnomAD4 exome AF: 0.0216 AC: 1993 AN: 92348 Hom.: 35 Cov.: 0 AF XY: 0.0208 AC XY: 975 AN XY: 46788

African (AFR) AF: 0.0411 AC: 131 AN: 3186

American (AMR) AF: 0.0129 AC: 34 AN: 2640

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 101 AN: 3724

East Asian (EAS) AF: 0.0223 AC: 181 AN: 8108

South Asian (SAS) AF: 0.0437 AC: 38 AN: 870

European-Finnish (FIN) AF: 0.00678 AC: 45 AN: 6634

Middle Eastern (MID) AF: 0.0378 AC: 19 AN: 502

European-Non Finnish (NFE) AF: 0.0213 AC: 1288 AN: 60342

Other (OTH) AF: 0.0246 AC: 156 AN: 6342

GnomAD4 genome AF: 0.0297 AC: 4514 AN: 152090 Hom.: 103 Cov.: 32 AF XY: 0.0290 AC XY: 2160 AN XY: 74378

African (AFR) AF: 0.0483 AC: 2008 AN: 41536

American (AMR) AF: 0.0164 AC: 251 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3472

East Asian (EAS) AF: 0.0401 AC: 205 AN: 5110

South Asian (SAS) AF: 0.0462 AC: 223 AN: 4828

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10592

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0225 AC: 1531 AN: 67942

Other (OTH) AF: 0.0285 AC: 60 AN: 2106

Alfa AF: 0.0241 Hom.: 10

Bravo AF: 0.0292

Asia WGS AF: 0.0340 AC: 118 AN: 3474

ClinVar

ClinVar submissions

Significance: Likely 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	-0.71
CADD	Benign	3.7
DANN	Benign	0.96
PhyloP100		-1.0
PromoterAI		-0.013	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs111484016; hg19: chr16-58497984;