rs10483442

chr14-33415344-C-Gchr14-33415344-C-T

Variant summary

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

The NM_001164749.2(NPAS3):c.468+48076C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,000 control chromosomes in the GnomAD database, including 3,262 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 0.20 (3262 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.468+48076C>G		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.468+48076C>G		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30157 AN: 151882 Hom.: 3255 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.199 AC: 30190 AN: 152000 Hom.: 3262 Cov.: 32 AF XY: 0.200 AC XY: 14833 AN XY: 74290

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0263

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.197

Alfa AF: 0.0802 Hom.: 102

Bravo AF: 0.208

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.9
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: rs10483442; hg19: chr14-33884550;