14-33448832-C-G

Variant names:

• chr14-33448832-C-G
• rs11845867
• NM_001164749.2:c.468+81564C>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.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
• Publications: 5 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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164749.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	NM_001164749.2	MANE Select	c.468+81564C>G		intron	N/A	NP_001158221.1	X5D2Q4
	NPAS3	NM_173159.3		c.429+81564C>G		intron	N/A	NP_775182.1	Q8IXF0-3
	NPAS3	NM_001394988.1		c.423+81564C>G		intron	N/A	NP_001381917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	ENST00000356141.9	TSL:1 MANE Select	c.468+81564C>G		intron	N/A	ENSP00000348460.4	Q8IXF0-1
	NPAS3	ENST00000357798.9	TSL:1	c.429+81564C>G		intron	N/A	ENSP00000350446.5	Q8IXF0-3
	NPAS3	ENST00000548645.5	TSL:1	c.378+81564C>G		intron	N/A	ENSP00000448916.1	Q8IXF0-2

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

African (AFR) AF: 0.542 AC: 22481 AN: 41452

American (AMR) AF: 0.684 AC: 10454 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2919 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4323 AN: 5158

South Asian (SAS) AF: 0.750 AC: 3610 AN: 4814

European-Finnish (FIN) AF: 0.686 AC: 7265 AN: 10590

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49266 AN: 68000

Other (OTH) AF: 0.718 AC: 1517 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		1.0
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: rs11845867; hg19: chr14-33918038;