rs4781679

Positions:

• chr16-15667576-C-G
• chr16-15667576-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017668.3(NDE1):​c.237+137C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,009,622 control chromosomes in the GnomAD database, including 227,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (40175 hom., cov: 27)
  • Exomes 𝑓: 0.66 (187712 hom.)
• Consequence: NDE1 NM_017668.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.227

Genes affected

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-15667576-C-G is Benign according to our data. Variant chr16-15667576-C-G is described in ClinVar as [Benign]. Clinvar id is 667639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDE1	NM_017668.3	c.237+137C>G		intron_variant		ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396354.6	c.237+137C>G		intron_variant		1	NM_017668.3	ENSP00000379642	P1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 108585 AN: 150066 Hom.: 40115 Cov.: 27

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.710

GnomAD4 exome AF: 0.657 AC: 564862 AN: 859440 Hom.: 187712 AF XY: 0.661 AC XY: 293364 AN XY: 443878

Gnomad4 AFR exome AF: 0.898

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.727

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.745

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome AF: 0.724 AC: 108706 AN: 150182 Hom.: 40175 Cov.: 27 AF XY: 0.724 AC XY: 52916 AN XY: 73114

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.710

Alfa AF: 0.698 Hom.: 4685

Bravo AF: 0.734

Asia WGS AF: 0.697 AC: 2424 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4781679; hg19: chr16-15761433;