14-33791429-C-T

Variant names:

• chr14-33791429-C-T
• rs1958058
• NM_001164749.2:c.1154-2468C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164749.2(NPAS3):​c.1154-2468C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,946 control chromosomes in the GnomAD database, including 12,367 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 0.40 (12367 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 7 publications found

Genes affected

NPAS3 (HGNC:19311): (neuronal PAS domain protein 3) This gene encodes a member of the basic helix-loop-helix and PAS domain-containing family of transcription factors. The encoded protein is localized to the nucleus and may regulate genes involved in neurogenesis. Chromosomal abnormalities that affect the coding potential of this gene are associated with schizophrenia and cognitive disability. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.1154-2468C>T		intron_variant	Intron 9 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.1154-2468C>T		intron_variant	Intron 9 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60583 AN: 151828 Hom.: 12365 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.399 AC: 60616 AN: 151946 Hom.: 12367 Cov.: 32 AF XY: 0.405 AC XY: 30062 AN XY: 74272

African (AFR) AF: 0.420 AC: 17407 AN: 41426

American (AMR) AF: 0.359 AC: 5475 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 945 AN: 3464

East Asian (EAS) AF: 0.532 AC: 2750 AN: 5166

South Asian (SAS) AF: 0.442 AC: 2131 AN: 4818

European-Finnish (FIN) AF: 0.511 AC: 5387 AN: 10540

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25471 AN: 67946

Other (OTH) AF: 0.367 AC: 776 AN: 2112

Alfa AF: 0.375 Hom.: 45913

Bravo AF: 0.390

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.41
PhyloP100		0.035
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: rs1958058; hg19: chr14-34260635;