16-58510391-G-C

Variant names:

• chr16-58510391-G-C
• rs246192
• NM_001242835.2:c.866-254G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001242835.2(NDRG4):​c.866-254G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,114 control chromosomes in the GnomAD database, including 31,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (31498 hom., cov: 33)
• Consequence: NDRG4 NM_001242835.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• Publications: 9 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=-0.93).
• BP6: Variant 16-58510391-G-C is Benign according to our data. Variant chr16-58510391-G-C is described in ClinVar as Benign. ClinVar VariationId is 1272101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242835.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	NM_001242835.2	MANE Select	c.866-254G>C		intron	N/A	NP_001229764.1
	NDRG4	NM_001378332.1		c.1112-254G>C		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.1076-254G>C		intron	N/A	NP_001365262.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000570248.6	TSL:1 MANE Select	c.866-254G>C		intron	N/A	ENSP00000457659.1
	NDRG4	ENST00000394282.8	TSL:1	c.1022-1031G>C		intron	N/A	ENSP00000377823.4
	NDRG4	ENST00000258187.9	TSL:1	c.962-1031G>C		intron	N/A	ENSP00000258187.5

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96029 AN: 151998 Hom.: 31453 Cov.: 33

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.632 AC: 96132 AN: 152114 Hom.: 31498 Cov.: 33 AF XY: 0.637 AC XY: 47364 AN XY: 74356

African (AFR) AF: 0.748 AC: 31028 AN: 41508

American (AMR) AF: 0.671 AC: 10260 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2304 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4920 AN: 5154

South Asian (SAS) AF: 0.762 AC: 3679 AN: 4826

European-Finnish (FIN) AF: 0.519 AC: 5491 AN: 10580

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36588 AN: 67968

Other (OTH) AF: 0.622 AC: 1314 AN: 2114

Alfa AF: 0.596 Hom.: 3469

Bravo AF: 0.646

Asia WGS AF: 0.840 AC: 2922 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.66
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs246192; hg19: chr16-58544295;