rs8004379

chr14-33599495-A-Cchr14-33599495-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001164749.2(NPAS3):c.558+39285A>C variant causes a intron change. The variant allele was found at a frequency of 0.123 in 152,186 control chromosomes in the GnomAD database, including 1,380 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 0.12 (1380 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.558+39285A>C		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.558+39285A>C		intron_variant		1	NM_001164749.2	A2
	ENST00000665335.1	n.117+1378T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18664 AN: 152068 Hom.: 1380 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.123 AC: 18668 AN: 152186 Hom.: 1380 Cov.: 32 AF XY: 0.129 AC XY: 9595 AN XY: 74406

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.119

Alfa AF: 0.104 Hom.: 1510

Bravo AF: 0.120

Asia WGS AF: 0.250 AC: 865 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	22
Dann	Benign	0.87

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: rs8004379; hg19: chr14-34068701;