chr14-33131632-T-C

Variant names:

• chr14-33131632-T-C
• rs10483426
• NM_001164749.2:c.140+75638T>C

Variant summary

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

The NM_001164749.2(NPAS3):​c.140+75638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,924 control chromosomes in the GnomAD database, including 19,024 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 0.49 (19024 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.140+75638T>C		intron_variant	Intron 2 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.140+75638T>C		intron_variant	Intron 2 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74890 AN: 151808 Hom.: 19012 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.493 AC: 74930 AN: 151924 Hom.: 19024 Cov.: 32 AF XY: 0.494 AC XY: 36667 AN XY: 74252

African (AFR) AF: 0.370 AC: 15344 AN: 41416

American (AMR) AF: 0.535 AC: 8164 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1697 AN: 3468

East Asian (EAS) AF: 0.406 AC: 2096 AN: 5166

South Asian (SAS) AF: 0.471 AC: 2266 AN: 4816

European-Finnish (FIN) AF: 0.543 AC: 5727 AN: 10548

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.558 AC: 37946 AN: 67954

Other (OTH) AF: 0.477 AC: 1005 AN: 2108

Alfa AF: 0.530 Hom.: 7860

Bravo AF: 0.491

Asia WGS AF: 0.427 AC: 1484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.66
PhyloP100		0.98
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: rs10483426; hg19: chr14-33600838;