rs4982029

Variant names:

• chr14-33007060-G-A
• rs4982029
• NM_001164749.2:c.51-48845G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.51-48845G>A		intron_variant	Intron 1 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.51-48845G>A		intron_variant	Intron 1 of 11	1	NM_001164749.2	ENSP00000348460.4

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

African (AFR) AF: 0.208 AC: 8623 AN: 41460

American (AMR) AF: 0.101 AC: 1544 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3470

East Asian (EAS) AF: 0.00425 AC: 22 AN: 5174

South Asian (SAS) AF: 0.0929 AC: 448 AN: 4822

European-Finnish (FIN) AF: 0.0889 AC: 941 AN: 10584

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2167 AN: 67998

Other (OTH) AF: 0.0762 AC: 161 AN: 2114

Alfa AF: 0.0485 Hom.: 1123

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
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4982029; hg19: chr14-33476266;