rs4781678

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDE1	NM_017668.3	c.-44+2961C>A		intron_variant	Intron 1 of 8	ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396354.6	c.-44+2961C>A		intron_variant	Intron 1 of 8	1	NM_017668.3	ENSP00000379642.1

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

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.632

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.028
DANN	Benign	0.80

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: rs4781678; hg19: chr16-15747112;