chr16-58494768-G-A

Variant names:

• chr16-58494768-G-A
• rs113878610
• ENST00000394282.8:c.133-196G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000394282.8(NDRG4):​c.133-196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0089 in 150,502 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.0089 (15 hom., cov: 31)
• Consequence: NDRG4 ENST00000394282.8 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.67
• 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-58494768-G-A is Benign according to our data. Variant chr16-58494768-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDRG4	NM_001378332.1	c.133-196G>A		intron_variant	Intron 2 of 17		NP_001365261.1
NDRG4	NM_001378333.1	c.133-196G>A		intron_variant	Intron 2 of 16		NP_001365262.1
NDRG4	NM_001378334.1	c.133-196G>A		intron_variant	Intron 2 of 16		NP_001365263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDRG4	ENST00000394282.8	c.133-196G>A		intron_variant	Intron 2 of 15	1		ENSP00000377823.4
NDRG4	ENST00000258187.9	c.73-196G>A		intron_variant	Intron 2 of 15	1		ENSP00000258187.5
NDRG4	ENST00000394279.6	c.73-196G>A		intron_variant	Intron 2 of 15	5		ENSP00000377820.2

Frequencies

GnomAD3 genomes AF: 0.00882 AC: 1327 AN: 150382 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00226

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.00524

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00725

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00890 AC: 1339 AN: 150502 Hom.: 15 Cov.: 31 AF XY: 0.00910 AC XY: 667 AN XY: 73324

African (AFR) AF: 0.00245 AC: 100 AN: 40822

American (AMR) AF: 0.0111 AC: 167 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 32 AN: 3466

East Asian (EAS) AF: 0.0130 AC: 66 AN: 5092

South Asian (SAS) AF: 0.00524 AC: 25 AN: 4768

European-Finnish (FIN) AF: 0.0158 AC: 160 AN: 10150

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0113 AC: 767 AN: 67846

Other (OTH) AF: 0.00861 AC: 18 AN: 2090

Alfa AF: 0.0129 Hom.: 2

Bravo AF: 0.00833

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 29, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.61
PhyloP100		-1.7
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: rs113878610; hg19: chr16-58528672;