rs8044738

chr16-15687197-A-Gchr16-15687197-A-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.387-178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,516,290 control chromosomes in the GnomAD database, including 334,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (40815 hom., cov: 31)
  • Exomes 𝑓: 0.65 (293373 hom.)
• Consequence: NDE1 NM_017668.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.379

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=-0.87).
• BP6: Variant 16-15687197-A-G is Benign according to our data. Variant chr16-15687197-A-G is described in ClinVar as [Benign]. Clinvar id is 667642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDE1	NM_017668.3	c.387-178A>G		intron_variant		ENST00000396354.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDE1	ENST00000396354.6	c.387-178A>G		intron_variant		1	NM_017668.3	P1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110147 AN: 151820 Hom.: 40753 Cov.: 31

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.713

GnomAD3 exomes AF: 0.691 AC: 96166 AN: 139152 Hom.: 33578 AF XY: 0.694 AC XY: 52159 AN XY: 75152

Gnomad AFR exome AF: 0.908

Gnomad AMR exome AF: 0.702

Gnomad ASJ exome AF: 0.728

Gnomad EAS exome AF: 0.645

Gnomad SAS exome AF: 0.749

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.642

Gnomad OTH exome AF: 0.689

GnomAD4 exome AF: 0.653 AC: 890870 AN: 1364352 Hom.: 293373 Cov.: 28 AF XY: 0.655 AC XY: 441284 AN XY: 673390

Gnomad4 AFR exome AF: 0.902

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.727

Gnomad4 EAS exome AF: 0.606

Gnomad4 SAS exome AF: 0.747

Gnomad4 FIN exome AF: 0.647

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.680

GnomAD4 genome AF: 0.726 AC: 110270 AN: 151938 Hom.: 40815 Cov.: 31 AF XY: 0.726 AC XY: 53909 AN XY: 74250

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.713

Alfa AF: 0.699 Hom.: 8585

Bravo AF: 0.735

Asia WGS AF: 0.697 AC: 2425 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	-0.87
Cadd	Benign	0.88
Dann	Benign	0.34

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: rs8044738; hg19: chr16-15781054; COSMIC: COSV61269821; COSMIC: COSV61269821;