rs7142052

Positions:

• chr14-33006392-C-T

Variant summary

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

The ENST00000356141.9(NPAS3):​c.51-49513C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,048 control chromosomes in the GnomAD database, including 1,473 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 0.10 (1473 hom., cov: 32)
• Consequence: NPAS3 ENST00000356141.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.51-49513C>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.51-49513C>T		intron_variant		1	NM_001164749.2	ENSP00000348460	A2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15917 AN: 151930 Hom.: 1471 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0906

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

GnomAD4 genome AF: 0.105 AC: 15935 AN: 152048 Hom.: 1473 Cov.: 32 AF XY: 0.104 AC XY: 7750 AN XY: 74346

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00426

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.0891

Gnomad4 NFE AF: 0.0323

Gnomad4 OTH AF: 0.0901

Alfa AF: 0.0474 Hom.: 489

Bravo AF: 0.114

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.9
DANN	Benign	0.42

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: rs7142052; hg19: chr14-33475598;