rs8015959

Positions:

• chr14-33011716-C-T

Variant summary

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

The NM_001164749.2(NPAS3):​c.51-44189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 152,100 control chromosomes in the GnomAD database, including 906 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 0.088 (906 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.51-44189C>T		intron_variant		ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.51-44189C>T		intron_variant		1	NM_001164749.2	ENSP00000348460	A2

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13342 AN: 151982 Hom.: 905 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0736

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

GnomAD4 genome AF: 0.0878 AC: 13356 AN: 152100 Hom.: 906 Cov.: 32 AF XY: 0.0881 AC XY: 6552 AN XY: 74364

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.0985

Gnomad4 FIN AF: 0.0891

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0367 Hom.: 336

Bravo AF: 0.0938

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.64

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: rs8015959; hg19: chr14-33480922;