14-33083528-T-C

Position:

• chr14-33083528-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164749.2(NPAS3):​c.140+27534T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,002 control chromosomes in the GnomAD database, including 15,781 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 0.43 (15781 hom., cov: 31)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.140+27534T>C		intron_variant		ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.140+27534T>C		intron_variant		1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65724 AN: 151884 Hom.: 15749 Cov.: 31

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.433 AC: 65803 AN: 152002 Hom.: 15781 Cov.: 31 AF XY: 0.433 AC XY: 32179 AN XY: 74310

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.421

Alfa AF: 0.350 Hom.: 7058

Bravo AF: 0.436

Asia WGS AF: 0.532 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs8014514; hg19: chr14-33552734;