rs4781679

Variant names:

• chr16-15667576-C-G
• rs4781679
• NM_017668.3:c.237+137C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• 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 -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 VariationId 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 rank	MANE	Protein	UniProt
NDE1	NM_017668.3	c.237+137C>G		intron_variant	Intron 3 of 8	ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396354.6	c.237+137C>G		intron_variant	Intron 3 of 8	1	NM_017668.3	ENSP00000379642.1

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

African (AFR) AF: 0.898 AC: 18973 AN: 21118

American (AMR) AF: 0.705 AC: 24556 AN: 34850

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 15782 AN: 21716

East Asian (EAS) AF: 0.603 AC: 20077 AN: 33296

South Asian (SAS) AF: 0.745 AC: 51478 AN: 69128

European-Finnish (FIN) AF: 0.648 AC: 24150 AN: 37296

Middle Eastern (MID) AF: 0.753 AC: 2289 AN: 3040

European-Non Finnish (NFE) AF: 0.635 AC: 379677 AN: 598298

Other (OTH) AF: 0.685 AC: 27880 AN: 40698

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

African (AFR) AF: 0.896 AC: 36567 AN: 40812

American (AMR) AF: 0.703 AC: 10500 AN: 14942

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2519 AN: 3468

East Asian (EAS) AF: 0.635 AC: 3227 AN: 5084

South Asian (SAS) AF: 0.742 AC: 3558 AN: 4792

European-Finnish (FIN) AF: 0.648 AC: 6500 AN: 10034

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.642 AC: 43480 AN: 67768

Other (OTH) AF: 0.710 AC: 1483 AN: 2088

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

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.23
Mutation Taster		=21/79	disease causing

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: rs4781679; hg19: chr16-15761433;