rs17555909

Variant names:

• chr14-33196733-T-C
• rs17555909
• NM_001164749.2:c.141-18449T>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.141-18449T>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
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	NM_001164749.2	MANE Select	c.141-18449T>C		intron	N/A	NP_001158221.1	X5D2Q4
	NPAS3	NM_173159.3		c.51-18449T>C		intron	N/A	NP_775182.1	Q8IXF0-3
	NPAS3	NM_001394988.1		c.51-18449T>C		intron	N/A	NP_001381917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	ENST00000356141.9	TSL:1 MANE Select	c.141-18449T>C		intron	N/A	ENSP00000348460.4	Q8IXF0-1
	NPAS3	ENST00000357798.9	TSL:1	c.51-18449T>C		intron	N/A	ENSP00000350446.5	Q8IXF0-3
	NPAS3	ENST00000548645.5	TSL:1	c.51-18449T>C		intron	N/A	ENSP00000448916.1	Q8IXF0-2

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

African (AFR) AF: 0.0206 AC: 855 AN: 41586

American (AMR) AF: 0.0705 AC: 1078 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5182

South Asian (SAS) AF: 0.0849 AC: 410 AN: 4828

European-Finnish (FIN) AF: 0.175 AC: 1851 AN: 10588

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8350 AN: 68012

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.108 Hom.: 1561

Bravo AF: 0.0749

Asia WGS AF: 0.0540 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.79
PhyloP100		-0.098
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: rs17555909; hg19: chr14-33665939;