rs11849533

Variant names:

• chr14-33570303-A-G
• rs11849533
• NM_001164749.2:c.558+10093A>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.558+10093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,042 control chromosomes in the GnomAD database, including 4,988 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 0.25 (4988 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 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.558+10093A>G		intron	N/A	NP_001158221.1	X5D2Q4
	NPAS3	NM_173159.3		c.519+10093A>G		intron	N/A	NP_775182.1	Q8IXF0-3
	NPAS3	NM_001394988.1		c.513+10093A>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.558+10093A>G		intron	N/A	ENSP00000348460.4	Q8IXF0-1
	NPAS3	ENST00000357798.9	TSL:1	c.519+10093A>G		intron	N/A	ENSP00000350446.5	Q8IXF0-3
	NPAS3	ENST00000548645.5	TSL:1	c.468+10093A>G		intron	N/A	ENSP00000448916.1	Q8IXF0-2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37323 AN: 151924 Hom.: 4986 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.246 AC: 37363 AN: 152042 Hom.: 4988 Cov.: 32 AF XY: 0.251 AC XY: 18650 AN XY: 74310

African (AFR) AF: 0.319 AC: 13208 AN: 41448

American (AMR) AF: 0.318 AC: 4864 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 800 AN: 3472

East Asian (EAS) AF: 0.378 AC: 1945 AN: 5152

South Asian (SAS) AF: 0.260 AC: 1251 AN: 4818

European-Finnish (FIN) AF: 0.228 AC: 2407 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12136 AN: 67990

Other (OTH) AF: 0.245 AC: 516 AN: 2110

Alfa AF: 0.228 Hom.: 1254

Bravo AF: 0.260

Asia WGS AF: 0.333 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.040
DANN	Benign	0.38
PhyloP100		-1.4
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: rs11849533; hg19: chr14-34039509;