rs1111533

Positions:

• chr14-33321403-A-C

Variant summary

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

The NM_001164749.2(NPAS3):​c.386-45783A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,974 control chromosomes in the GnomAD database, including 1,510 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 (1510 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.386-45783A>C		intron_variant		ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.386-45783A>C		intron_variant		1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17835 AN: 151856 Hom.: 1502 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0942

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0638

Gnomad OTH AF: 0.0947

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

GnomAD4 genome AF: 0.118 AC: 17872 AN: 151974 Hom.: 1510 Cov.: 32 AF XY: 0.120 AC XY: 8895 AN XY: 74294

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0600

Gnomad4 ASJ AF: 0.0401

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0942

Gnomad4 NFE AF: 0.0638

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.0724 Hom.: 770

Bravo AF: 0.121

Asia WGS AF: 0.225 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.70

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: rs1111533; hg19: chr14-33790609;