Variant rs8044738 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.379

Variant links:

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]

NDE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
NDE1	NM_017668.3 linkuse as main transcript	c.387-178A>G		intron_variant		ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396354.6 linkuse as main transcript	c.387-178A>G		intron_variant		1	NM_017668.3	ENSP00000379642	P1	Q9NXR1-2

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110147

AN:

151820

Hom.:

40753

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.655

AC XY:

441284

AN XY:

673390

show subpopulations

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.:

AF XY:

0.726

AC XY:

53909

AN XY:

74250

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over