chr16-58494832-T-TA

Variant names:

• chr16-58494832-T-TA
• rs59711785
• ENST00000394282.8:c.133-132_133-131insA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001378332.1(NDRG4):​c.133-117dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 531,574 control chromosomes in the GnomAD database, including 159 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (105 hom., cov: 0)
  • Exomes 𝑓: 0.19 (54 hom.)
• Consequence: NDRG4 NM_001378332.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.525
• 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 -10 ACMG points.

• BP6: Variant 16-58494832-T-TA is Benign according to our data. Variant chr16-58494832-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1276866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378332.1. 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_001378332.1		c.133-117dupA		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.133-117dupA		intron	N/A	NP_001365262.1
	NDRG4	NM_001378334.1		c.133-117dupA		intron	N/A	NP_001365263.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000394282.8	TSL:1	c.133-132_133-131insA		intron	N/A	ENSP00000377823.4	Q9ULP0-6
	NDRG4	ENST00000258187.9	TSL:1	c.73-132_73-131insA		intron	N/A	ENSP00000258187.5	Q9ULP0-3
	NDRG4	ENST00000394279.6	TSL:5	c.73-132_73-131insA		intron	N/A	ENSP00000377820.2	Q9ULP0-3

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2663 AN: 135008 Hom.: 103 Cov.: 0

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00181

Gnomad EAS AF: 0.00150

Gnomad SAS AF: 0.00148

Gnomad FIN AF: 0.00724

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.00272

Gnomad OTH AF: 0.0161

GnomAD4 exome AF: 0.187 AC: 74246 AN: 396588 Hom.: 54 AF XY: 0.186 AC XY: 38614 AN XY: 207430

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.234 AC: 2460 AN: 10504

American (AMR) AF: 0.226 AC: 3587 AN: 15882

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 1987 AN: 11048

East Asian (EAS) AF: 0.187 AC: 4905 AN: 26188

South Asian (SAS) AF: 0.174 AC: 6006 AN: 34486

European-Finnish (FIN) AF: 0.175 AC: 4213 AN: 24076

Middle Eastern (MID) AF: 0.191 AC: 385 AN: 2012

European-Non Finnish (NFE) AF: 0.186 AC: 46596 AN: 250942

Other (OTH) AF: 0.191 AC: 4107 AN: 21450

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0198 AC: 2673 AN: 134986 Hom.: 105 Cov.: 0 AF XY: 0.0202 AC XY: 1299 AN XY: 64370

African (AFR) AF: 0.0620 AC: 2252 AN: 36326

American (AMR) AF: 0.0111 AC: 150 AN: 13476

Ashkenazi Jewish (ASJ) AF: 0.00181 AC: 6 AN: 3316

East Asian (EAS) AF: 0.00150 AC: 7 AN: 4658

South Asian (SAS) AF: 0.00149 AC: 6 AN: 4018

European-Finnish (FIN) AF: 0.00724 AC: 48 AN: 6630

Middle Eastern (MID) AF: 0.00388 AC: 1 AN: 258

European-Non Finnish (NFE) AF: 0.00272 AC: 173 AN: 63624

Other (OTH) AF: 0.0166 AC: 30 AN: 1808

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		-0.53
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: rs59711785; hg19: chr16-58528736;