rs11849533

Positions:

• chr14-33570303-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.558+10093A>G		intron_variant		ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.558+10093A>G		intron_variant		1	NM_001164749.2	ENSP00000348460	A2

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

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.245

Alfa AF: 0.226 Hom.: 1204

Bravo AF: 0.260

Asia WGS AF: 0.333 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.040
DANN	Benign	0.38

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: rs11849533; hg19: chr14-34039509;