14-33197521-T-C

Variant names:

• chr14-33197521-T-C
• rs4981180
• NM_001164749.2:c.141-17661T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164749.2(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 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164749.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	NM_001164749.2	MANE Select	c.141-17661T>C		intron	N/A	NP_001158221.1
	NPAS3	NM_173159.3		c.51-17661T>C		intron	N/A	NP_775182.1
	NPAS3	NM_001394988.1		c.51-17661T>C		intron	N/A	NP_001381917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	ENST00000356141.9	TSL:1 MANE Select	c.141-17661T>C		intron	N/A	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.51-17661T>C		intron	N/A	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.51-17661T>C		intron	N/A	ENSP00000448916.1

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

African (AFR) AF: 0.882 AC: 36441 AN: 41330

American (AMR) AF: 0.973 AC: 14843 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3457 AN: 3472

East Asian (EAS) AF: 0.872 AC: 4469 AN: 5126

South Asian (SAS) AF: 0.971 AC: 4649 AN: 4790

European-Finnish (FIN) AF: 0.993 AC: 10431 AN: 10500

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.982 AC: 66695 AN: 67948

Other (OTH) AF: 0.959 AC: 2023 AN: 2110

Alfa AF: 0.971 Hom.: 83842

Bravo AF: 0.946

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.67
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4981180; hg19: chr14-33666727;