rs17555909

Positions:

• chr14-33196733-T-C

Variant summary

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

The NM_001164749.2(NPAS3):​c.141-18449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,274 control chromosomes in the GnomAD database, including 785 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 0.087 (785 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.141-18449T>C		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.141-18449T>C		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13257 AN: 152156 Hom.: 785 Cov.: 33

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0823

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

GnomAD4 genome AF: 0.0871 AC: 13258 AN: 152274 Hom.: 785 Cov.: 33 AF XY: 0.0889 AC XY: 6618 AN XY: 74452

Gnomad4 AFR AF: 0.0206

Gnomad4 AMR AF: 0.0705

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.0849

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.112 Hom.: 1310

Bravo AF: 0.0749

Asia WGS AF: 0.0540 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.79

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: rs17555909; hg19: chr14-33665939;