chr16-15643418-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001143979.2(NDE1):c.-675G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00655 in 468,038 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 33 hom. )

Consequence

NDE1
NM_001143979.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0240

Publications

3 publications found

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:

MARF1 (HGNC:29562): (meiosis regulator and mRNA stability factor 1) This gene encodes a putative peroxisomal protein that appears to be conserved across Euteleostomi. In humans, it may be autoantigenic. [provided by RefSeq, Jul 2010]

MARF1 links:

MIR484 (HGNC:32341): (microRNA 484) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR484 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 16-15643418-G-A is Benign according to our data. Variant chr16-15643418-G-A is described in ClinVar as Benign. ClinVar VariationId is 318020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00543 (827/152308) while in subpopulation SAS AF = 0.0251 (121/4824). AF 95% confidence interval is 0.0215. There are 12 homozygotes in GnomAd4. There are 445 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143979.2. 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_001143979.2		c.-675G>A		5_prime_UTR	Exon 1 of 10	NP_001137451.1	Q9NXR1-2
	MIR484	NR_030159.1		n.*46G>A		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDE1	ENST00000396355.5	TSL:1	c.-675G>A	5_prime_UTR	Exon 1 of 10	ENSP00000379643.1	Q9NXR1-2
NDE1	ENST00000911227.1		c.-553G>A	5_prime_UTR	Exon 1 of 9	ENSP00000581286.1
MARF1	ENST00000892732.1		c.-459C>T	upstream_gene	N/A	ENSP00000562791.1

Frequencies

GnomAD3 genomes

AF:

0.00533

AC:

811

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00732

Gnomad SAS

AF:

0.0251

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00728

AC:

1125

AN:

154572

AF XY:

0.00873

show subpopulations

Gnomad AFR exome

AF:

0.00543

Gnomad AMR exome

AF:

0.00499

Gnomad ASJ exome

AF:

0.00841

Gnomad EAS exome

AF:

0.0118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00330

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.00709

AC:

2237

AN:

315730

Hom.:

Cov.:

AF XY:

0.00886

AC XY:

1600

AN XY:

180544

show subpopulations

African (AFR)

AF:

0.00654

AC:

AN:

7032

American (AMR)

AF:

0.00448

AC:

115

AN:

25690

Ashkenazi Jewish (ASJ)

AF:

0.00780

AC:

AN:

10510

East Asian (EAS)

AF:

0.0111

AC:

AN:

8498

South Asian (SAS)

AF:

0.0225

AC:

1330

AN:

59204

European-Finnish (FIN)

AF:

0.000140

AC:

AN:

28664

Middle Eastern (MID)

AF:

0.00253

AC:

AN:

2764

European-Non Finnish (NFE)

AF:

0.00291

AC:

464

AN:

159238

Other (OTH)

AF:

0.00672

AC:

AN:

14130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

120

240

359

479

599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00543

AC:

827

AN:

152308

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

445

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00592

AC:

246

AN:

41562

American (AMR)

AF:

0.0107

AC:

164

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00733

AC:

AN:

5182

South Asian (SAS)

AF:

0.0251

AC:

121

AN:

4824

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00278

AC:

189

AN:

68024

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00394

Hom.:

Bravo

AF:

0.00525

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Lissencephaly 4 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.024

PromoterAI

0.0084

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over