rs974002

chr14-33105464-A-G

Variant summary

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

The NM_001164749.2(NPAS3):c.140+49470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,086 control chromosomes in the GnomAD database, including 2,513 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 0.17 (2513 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.140+49470A>G		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.140+49470A>G		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25833 AN: 151968 Hom.: 2518 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.170 AC: 25833 AN: 152086 Hom.: 2513 Cov.: 32 AF XY: 0.173 AC XY: 12885 AN XY: 74316

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.187

Alfa AF: 0.182 Hom.: 5535

Bravo AF: 0.163

Asia WGS AF: 0.380 AC: 1317 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.0
Dann	Benign	0.63

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: rs974002; hg19: chr14-33574670;