14-33671679-T-C

Variant names:

• chr14-33671679-T-C
• rs7141612
• NM_001164749.2:c.559-4532T>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.559-4532T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,102 control chromosomes in the GnomAD database, including 35,637 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 0.68 (35637 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 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.559-4532T>C		intron	N/A	NP_001158221.1
	NPAS3	NM_173159.3		c.520-4532T>C		intron	N/A	NP_775182.1
	NPAS3	NM_001394988.1		c.514-4532T>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.559-4532T>C		intron	N/A	ENSP00000348460.4
	NPAS3	ENST00000357798.9	TSL:1	c.520-4532T>C		intron	N/A	ENSP00000350446.5
	NPAS3	ENST00000548645.5	TSL:1	c.469-4532T>C		intron	N/A	ENSP00000448916.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103646 AN: 151982 Hom.: 35602 Cov.: 33

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.682 AC: 103741 AN: 152102 Hom.: 35637 Cov.: 33 AF XY: 0.679 AC XY: 50466 AN XY: 74336

African (AFR) AF: 0.778 AC: 32289 AN: 41506

American (AMR) AF: 0.649 AC: 9921 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3468

East Asian (EAS) AF: 0.638 AC: 3294 AN: 5164

South Asian (SAS) AF: 0.710 AC: 3424 AN: 4824

European-Finnish (FIN) AF: 0.580 AC: 6126 AN: 10570

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44212 AN: 67972

Other (OTH) AF: 0.684 AC: 1448 AN: 2116

Alfa AF: 0.660 Hom.: 127892

Bravo AF: 0.688

Asia WGS AF: 0.678 AC: 2355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.51
PhyloP100		1.3
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: rs7141612; hg19: chr14-34140885;