rs363172

Variant names:

• chr16-66811121-G-A
• rs363172
• NM_003905.4:c.1035-349C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-66811121-G-A
• chr16-66811121-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003905.4(NAE1):​c.1035-349C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,032 control chromosomes in the GnomAD database, including 8,553 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 0.31 (8553 hom., cov: 32)
• Consequence: NAE1 NM_003905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 4 publications found

Genes affected

NAE1 (HGNC:621): (NEDD8 activating enzyme E1 subunit 1) The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer's disease. In addition, the encoded protein can form a heterodimer with UBE1C and bind and activate NEDD8, a ubiquitin-like protein. This protein is required for cell cycle progression through the S/M checkpoint. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

NAE1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003905.4. 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
	NAE1	NM_003905.4	MANE Select	c.1035-349C>T		intron	N/A	NP_003896.1	Q13564-1
	NAE1	NM_001286500.2		c.1044-349C>T		intron	N/A	NP_001273429.1	Q13564-4
	NAE1	NM_001018159.2		c.1017-349C>T		intron	N/A	NP_001018169.1	Q13564-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAE1	ENST00000290810.8	TSL:1 MANE Select	c.1035-349C>T		intron	N/A	ENSP00000290810.3	Q13564-1
	NAE1	ENST00000934206.1		c.1035-349C>T		intron	N/A	ENSP00000604265.1
	NAE1	ENST00000359087.8	TSL:2	c.1044-349C>T		intron	N/A	ENSP00000351990.4	Q13564-4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47004 AN: 151914 Hom.: 8546 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.309 AC: 47027 AN: 152032 Hom.: 8553 Cov.: 32 AF XY: 0.315 AC XY: 23412 AN XY: 74316

African (AFR) AF: 0.122 AC: 5067 AN: 41496

American (AMR) AF: 0.417 AC: 6370 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1652 AN: 3466

East Asian (EAS) AF: 0.600 AC: 3096 AN: 5156

South Asian (SAS) AF: 0.418 AC: 2014 AN: 4814

European-Finnish (FIN) AF: 0.353 AC: 3735 AN: 10568

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23866 AN: 67942

Other (OTH) AF: 0.346 AC: 730 AN: 2112

Alfa AF: 0.309 Hom.: 1057

Bravo AF: 0.310

Asia WGS AF: 0.475 AC: 1650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		0.083
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: rs363172; hg19: chr16-66845024;