16-58463938-C-T

Variant names:

• chr16-58463938-C-T
• rs560239722
• ENST00000258187.9:c.-24+141C>T

Variant summary

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

The NM_001378338.1(NDRG4):​c.-24+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 151,136 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (16 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDRG4 NM_001378338.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 16-58463938-C-T is Benign according to our data. Variant chr16-58463938-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1317199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00576 (870/151136) while in subpopulation AFR AF = 0.0203 (836/41270). AF 95% confidence interval is 0.0191. There are 16 homozygotes in GnomAd4. There are 411 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378338.1. 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+141C>T		intron	N/A	NP_001365267.1
	NDRG4	NM_001378339.1		c.-24+141C>T		intron	N/A	NP_001365268.1
	NDRG4	NM_001378342.1		c.-24+141C>T		intron	N/A	NP_001365271.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000258187.9	TSL:1	c.-24+141C>T		intron	N/A	ENSP00000258187.5	Q9ULP0-3
	NDRG4	ENST00000889964.1		c.-165+141C>T		intron	N/A	ENSP00000560023.1
	NDRG4	ENST00000961840.1		c.-302+141C>T		intron	N/A	ENSP00000631899.1

Frequencies

GnomAD3 genomes AF: 0.00575 AC: 869 AN: 151026 Hom.: 16 Cov.: 30

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000592

Gnomad OTH AF: 0.00337

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1310 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 656

African (AFR) AF: 0.00 AC: 0 AN: 48

American (AMR) AF: 0.00 AC: 0 AN: 18

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 36

East Asian (EAS) AF: 0.00 AC: 0 AN: 56

South Asian (SAS) AF: 0.00 AC: 0 AN: 508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 578

Other (OTH) AF: 0.00 AC: 0 AN: 42

GnomAD4 genome AF: 0.00576 AC: 870 AN: 151136 Hom.: 16 Cov.: 30 AF XY: 0.00556 AC XY: 411 AN XY: 73896

African (AFR) AF: 0.0203 AC: 836 AN: 41270

American (AMR) AF: 0.00151 AC: 23 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5044

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000592 AC: 4 AN: 67608

Other (OTH) AF: 0.00333 AC: 7 AN: 2102

Alfa AF: 0.00458 Hom.: 1

Bravo AF: 0.00644

Asia WGS AF: 0.000581 AC: 2 AN: 3454

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	-0.74
CADD	Benign	9.2
DANN	Benign	0.82
PhyloP100		0.11
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs560239722; hg19: chr16-58497842;