rs4781678

Variant names:

• chr16-15653255-C-A
• rs4781678
• NM_017668.3:c.-44+2961C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017668.3(NDE1):​c.-44+2961C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,042 control chromosomes in the GnomAD database, including 33,363 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33363 hom., cov: 32)
• Consequence: NDE1 NM_017668.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• lissencephaly 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Ambry Genetics
• microcephaly with lissencephaly and/or hydranencephaly

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hydranencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microlissencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• NDE1-related microhydranencephaly

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017668.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDE1	NM_017668.3	MANE Select	c.-44+2961C>A		intron	N/A	NP_060138.1	Q9NXR1-2
	NDE1	NM_001143979.2		c.-44+3786C>A		intron	N/A	NP_001137451.1	Q9NXR1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDE1	ENST00000396354.6	TSL:1 MANE Select	c.-44+2961C>A		intron	N/A	ENSP00000379642.1	Q9NXR1-2
	NDE1	ENST00000396355.5	TSL:1	c.-44+3786C>A		intron	N/A	ENSP00000379643.1	Q9NXR1-2
	NDE1	ENST00000911227.1		c.-44+9328C>A		intron	N/A	ENSP00000581286.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98760 AN: 151924 Hom.: 33316 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.650 AC: 98868 AN: 152042 Hom.: 33363 Cov.: 32 AF XY: 0.652 AC XY: 48436 AN XY: 74302

African (AFR) AF: 0.835 AC: 34632 AN: 41496

American (AMR) AF: 0.632 AC: 9645 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2242 AN: 3468

East Asian (EAS) AF: 0.364 AC: 1878 AN: 5154

South Asian (SAS) AF: 0.614 AC: 2964 AN: 4824

European-Finnish (FIN) AF: 0.621 AC: 6556 AN: 10564

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38791 AN: 67970

Other (OTH) AF: 0.632 AC: 1335 AN: 2112

Alfa AF: 0.647 Hom.: 6410

Bravo AF: 0.658

Asia WGS AF: 0.497 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.028
DANN	Benign	0.80
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4781678; hg19: chr16-15747112;