rs974002

Variant names:

• chr14-33105464-A-G
• rs974002
• NM_001164749.2:c.140+49470A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.86).
• 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 rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.140+49470A>G		intron_variant	Intron 2 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.140+49470A>G		intron_variant	Intron 2 of 11	1	NM_001164749.2	ENSP00000348460.4

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

African (AFR) AF: 0.122 AC: 5053 AN: 41536

American (AMR) AF: 0.131 AC: 1993 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3472

East Asian (EAS) AF: 0.435 AC: 2242 AN: 5152

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4818

European-Finnish (FIN) AF: 0.152 AC: 1612 AN: 10572

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11784 AN: 67958

Other (OTH) AF: 0.187 AC: 395 AN: 2114

Alfa AF: 0.179 Hom.: 11637

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
PhyloP100		-0.063
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: rs974002; hg19: chr14-33574670;