NM_001164749.2:c.468+48076C>G

Variant names:

• chr14-33415344-C-G
• rs10483442
• NM_001164749.2:c.468+48076C>G

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+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
• 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=-0.88).
• 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 rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.468+48076C>G		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+48076C>G		intron_variant	Intron 4 of 11	1	NM_001164749.2	ENSP00000348460.4

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

African (AFR) AF: 0.236 AC: 9767 AN: 41438

American (AMR) AF: 0.277 AC: 4223 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3470

East Asian (EAS) AF: 0.0263 AC: 136 AN: 5164

South Asian (SAS) AF: 0.136 AC: 656 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2150 AN: 10554

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12113 AN: 67978

Other (OTH) AF: 0.197 AC: 416 AN: 2110

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
PhyloP100		-0.14
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: rs10483442; hg19: chr14-33884550;