rs4791707

Positions:

• chr17-8462845-C-T

Variant summary

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

The NM_030808.5(NDEL1):​c.944+2685C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 154,914 control chromosomes in the GnomAD database, including 12,061 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 0.39 (11834 hom., cov: 33)
  • Exomes 𝑓: 0.39 (227 hom.)
• Consequence: NDEL1 NM_030808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

Genes affected

NDEL1 (HGNC:17620): (nudE neurodevelopment protein 1 like 1) Enables identical protein binding activity. Involved in chromosome segregation; positive regulation of GTPase activity; and regulation of intracellular protein transport. Located in kinetochore. Biomarker of schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDEL1	NM_030808.5	c.944+2685C>T		intron_variant		ENST00000334527.12	NP_110435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDEL1	ENST00000334527.12	c.944+2685C>T		intron_variant		1	NM_030808.5	ENSP00000333982.7

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59972 AN: 152024 Hom.: 11819 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.386 AC: 1069 AN: 2772 Hom.: 227 Cov.: 0 AF XY: 0.383 AC XY: 550 AN XY: 1436

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.416

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.394 AC: 60018 AN: 152142 Hom.: 11834 Cov.: 33 AF XY: 0.397 AC XY: 29500 AN XY: 74372

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.388

Alfa AF: 0.400 Hom.: 1948

Bravo AF: 0.390

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.73
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: rs4791707; hg19: chr17-8366163;