14-33197521-T-C

Position:

• chr14-33197521-T-C

Variant summary

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

The ENST00000356141.9(NPAS3):​c.141-17661T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 151,740 control chromosomes in the GnomAD database, including 68,685 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 0.95 (68685 hom., cov: 28)
• Consequence: NPAS3 ENST00000356141.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.141-17661T>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.141-17661T>C		intron_variant		1	NM_001164749.2	ENSP00000348460	A2

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144097 AN: 151624 Hom.: 68633 Cov.: 28

Gnomad AFR AF: 0.881

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.961

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

GnomAD4 genome AF: 0.950 AC: 144205 AN: 151740 Hom.: 68685 Cov.: 28 AF XY: 0.951 AC XY: 70507 AN XY: 74134

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.973

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.982

Gnomad4 OTH AF: 0.959

Alfa AF: 0.974 Hom.: 63118

Bravo AF: 0.946

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.67

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: rs4981180; hg19: chr14-33666727;