16-66808891-A-T

Position:

• chr16-66808891-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003905.4(NAE1):​c.1237+98T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 739,290 control chromosomes in the GnomAD database, including 85,709 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 0.51 (20848 hom., cov: 33)
  • Exomes 𝑓: 0.46 (64861 hom.)
• Consequence: NAE1 NM_003905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAE1	NM_003905.4	c.1237+98T>A		intron_variant		ENST00000290810.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAE1	ENST00000290810.8	c.1237+98T>A		intron_variant		1	NM_003905.4	P3

Frequencies

GnomAD3 genomes AF: 0.514 AC: 77990 AN: 151860 Hom.: 20811 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.464 AC: 272301 AN: 587312 Hom.: 64861 Cov.: 8 AF XY: 0.467 AC XY: 141233 AN XY: 302174

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.514 AC: 78086 AN: 151978 Hom.: 20848 Cov.: 33 AF XY: 0.516 AC XY: 38318 AN XY: 74304

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.509

Alfa AF: 0.465 Hom.: 2129

Bravo AF: 0.525

Asia WGS AF: 0.625 AC: 2160 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs363169; hg19: chr16-66842794;