rs7147983

Variant names:

• chr14-33563077-G-C
• rs7147983
• NM_001164749.2:c.558+2867G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-33563077-G-C
• chr14-33563077-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164749.2(NPAS3):​c.558+2867G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,076 control chromosomes in the GnomAD database, including 49,078 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 0.80 (49078 hom., cov: 31)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.558+2867G>C		intron_variant	Intron 5 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.558+2867G>C		intron_variant	Intron 5 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.803 AC: 121949 AN: 151958 Hom.: 49034 Cov.: 31

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.803 AC: 122049 AN: 152076 Hom.: 49078 Cov.: 31 AF XY: 0.798 AC XY: 59366 AN XY: 74356

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.811

Alfa AF: 0.767 Hom.: 2320

Bravo AF: 0.808

Asia WGS AF: 0.758 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.37
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs7147983; hg19: chr14-34032283;