rs8007613

Variant names:

• chr14-33060989-A-G
• rs8007613
• NM_001164749.2:c.140+4995A>G

Variant summary

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

The NM_001164749.2(NPAS3):​c.140+4995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,128 control chromosomes in the GnomAD database, including 5,472 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 0.27 (5472 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.140+4995A>G		intron_variant	Intron 2 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.140+4995A>G		intron_variant	Intron 2 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40463 AN: 152010 Hom.: 5465 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.266 AC: 40515 AN: 152128 Hom.: 5472 Cov.: 33 AF XY: 0.266 AC XY: 19787 AN XY: 74378

African (AFR) AF: 0.276 AC: 11449 AN: 41512

American (AMR) AF: 0.298 AC: 4551 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 981 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1040 AN: 5156

South Asian (SAS) AF: 0.307 AC: 1483 AN: 4828

European-Finnish (FIN) AF: 0.205 AC: 2169 AN: 10588

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17962 AN: 67992

Other (OTH) AF: 0.256 AC: 539 AN: 2106

Alfa AF: 0.269 Hom.: 9648

Bravo AF: 0.273

Asia WGS AF: 0.270 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.44
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: rs8007613; hg19: chr14-33530195;