rs4503707

Variant names:

• chr14-33402851-C-T
• rs4503707
• NM_001164749.2:c.468+35583C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164749.2(NPAS3):​c.468+35583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,132 control chromosomes in the GnomAD database, including 3,434 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 (3434 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 2 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 = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.468+35583C>T		intron_variant	Intron 4 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.468+35583C>T		intron_variant	Intron 4 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29820 AN: 152014 Hom.: 3421 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0334

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.196 AC: 29873 AN: 152132 Hom.: 3434 Cov.: 33 AF XY: 0.197 AC XY: 14687 AN XY: 74378

African (AFR) AF: 0.293 AC: 12164 AN: 41520

American (AMR) AF: 0.263 AC: 4010 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3466

East Asian (EAS) AF: 0.0331 AC: 171 AN: 5162

South Asian (SAS) AF: 0.116 AC: 562 AN: 4826

European-Finnish (FIN) AF: 0.164 AC: 1739 AN: 10608

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10179 AN: 67966

Other (OTH) AF: 0.196 AC: 414 AN: 2114

Alfa AF: 0.0932 Hom.: 139

Bravo AF: 0.210

Asia WGS AF: 0.0810 AC: 286 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-0.23
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: rs4503707; hg19: chr14-33872057;