rs12100538

chr14-33411008-A-G

Variant summary

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

The NM_001164749.2(NPAS3):c.468+43740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,948 control chromosomes in the GnomAD database, including 16,626 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 0.45 (16626 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.468+43740A>G		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.468+43740A>G		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68917 AN: 151830 Hom.: 16573 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.454 AC: 69034 AN: 151948 Hom.: 16626 Cov.: 32 AF XY: 0.458 AC XY: 33964 AN XY: 74238

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.445

Alfa AF: 0.391 Hom.: 6019

Bravo AF: 0.475

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.4
Dann	Benign	0.46

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: rs12100538; hg19: chr14-33880214;