rs11845867

Positions:

• chr14-33448832-C-G

Variant summary

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

The NM_001164749.2(NPAS3):​c.468+81564C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,074 control chromosomes in the GnomAD database, including 35,447 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 0.68 (35447 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.468+81564C>G		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.468+81564C>G		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102762 AN: 151956 Hom.: 35439 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.676 AC: 102808 AN: 152074 Hom.: 35447 Cov.: 32 AF XY: 0.675 AC XY: 50200 AN XY: 74340

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.718

Alfa AF: 0.697 Hom.: 4635

Bravo AF: 0.671

Asia WGS AF: 0.784 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.66

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: rs11845867; hg19: chr14-33918038;