rs4982029

chr14-33007060-G-A

Variant summary

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

The NM_001164749.2(NPAS3):c.51-48845G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 152,106 control chromosomes in the GnomAD database, including 1,085 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 0.092 (1085 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS3	NM_001164749.2	c.51-48845G>A		intron_variant		ENST00000356141.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS3	ENST00000356141.9	c.51-48845G>A		intron_variant		1	NM_001164749.2	A2

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14028 AN: 151988 Hom.: 1084 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0889

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0765

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

GnomAD4 genome AF: 0.0923 AC: 14044 AN: 152106 Hom.: 1085 Cov.: 33 AF XY: 0.0923 AC XY: 6860 AN XY: 74356

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.0929

Gnomad4 FIN AF: 0.0889

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0387 Hom.: 284

Bravo AF: 0.0999

Asia WGS AF: 0.0700 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.82
Dann	Benign	0.38

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: rs4982029; hg19: chr14-33476266;