rs8006023

Variant names:

• chr14-33741804-G-A
• rs8006023
• NM_001164749.2:c.852+6472G>A

Variant summary

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

The NM_001164749.2(NPAS3):​c.852+6472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,032 control chromosomes in the GnomAD database, including 3,554 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 0.14 (3554 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 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.852+6472G>A		intron	N/A	NP_001158221.1	X5D2Q4
	NPAS3	NM_173159.3		c.813+6472G>A		intron	N/A	NP_775182.1	Q8IXF0-3
	NPAS3	NM_001394988.1		c.807+6472G>A		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.852+6472G>A		intron	N/A	ENSP00000348460.4	Q8IXF0-1
	NPAS3	ENST00000357798.9	TSL:1	c.813+6472G>A		intron	N/A	ENSP00000350446.5	Q8IXF0-3
	NPAS3	ENST00000548645.5	TSL:1	c.762+6472G>A		intron	N/A	ENSP00000448916.1	Q8IXF0-2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21461 AN: 151914 Hom.: 3522 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.142 AC: 21549 AN: 152032 Hom.: 3554 Cov.: 32 AF XY: 0.138 AC XY: 10249 AN XY: 74278

African (AFR) AF: 0.403 AC: 16695 AN: 41416

American (AMR) AF: 0.0852 AC: 1302 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3466

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.0378 AC: 182 AN: 4814

European-Finnish (FIN) AF: 0.0268 AC: 284 AN: 10584

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.0385 AC: 2620 AN: 68000

Other (OTH) AF: 0.112 AC: 237 AN: 2108

Alfa AF: 0.112 Hom.: 415

Bravo AF: 0.158

Asia WGS AF: 0.0470 AC: 167 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.29
PhyloP100		0.54
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: rs8006023; hg19: chr14-34211010;