rs1952161

Positions:

• chr14-33726120-C-G

Variant summary

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

The NM_001164749.2(NPAS3):​c.734-9094C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,890 control chromosomes in the GnomAD database, including 13,372 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 0.40 (13372 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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 (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.734-9094C>G		intron_variant		ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.734-9094C>G		intron_variant		1	NM_001164749.2	ENSP00000348460	A2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60944 AN: 151772 Hom.: 13359 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.402 AC: 61009 AN: 151890 Hom.: 13372 Cov.: 32 AF XY: 0.407 AC XY: 30193 AN XY: 74232

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.394

Alfa AF: 0.338 Hom.: 1320

Bravo AF: 0.424

Asia WGS AF: 0.499 AC: 1733 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	0.87
DANN	Benign	0.63

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: rs1952161; hg19: chr14-34195326;