chr14-33553627-T-C

Variant names:

• chr14-33553627-T-C
• rs10142154
• NM_001164749.2:c.469-6494T>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.469-6494T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,026 control chromosomes in the GnomAD database, including 10,038 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 0.35 (10038 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.469-6494T>C		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.469-6494T>C		intron_variant	Intron 4 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53468 AN: 151908 Hom.: 10028 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.352 AC: 53503 AN: 152026 Hom.: 10038 Cov.: 33 AF XY: 0.352 AC XY: 26136 AN XY: 74290

African (AFR) AF: 0.487 AC: 20181 AN: 41436

American (AMR) AF: 0.313 AC: 4780 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3468

East Asian (EAS) AF: 0.189 AC: 978 AN: 5178

South Asian (SAS) AF: 0.289 AC: 1390 AN: 4810

European-Finnish (FIN) AF: 0.312 AC: 3294 AN: 10574

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20293 AN: 67982

Other (OTH) AF: 0.337 AC: 711 AN: 2108

Alfa AF: 0.314 Hom.: 6515

Bravo AF: 0.359

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.093
DANN	Benign	0.70
PhyloP100		-0.76
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: rs10142154; hg19: chr14-34022833;