14-33360114-C-T

Variant names:

• chr14-33360114-C-T
• rs2274511
• NM_001164749.2:c.386-7072C>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.386-7072C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,214 control chromosomes in the GnomAD database, including 2,198 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 0.15 (2198 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.74
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.386-7072C>T		intron_variant	Intron 3 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.386-7072C>T		intron_variant	Intron 3 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23480 AN: 152094 Hom.: 2194 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.154 AC: 23511 AN: 152214 Hom.: 2198 Cov.: 32 AF XY: 0.151 AC XY: 11218 AN XY: 74408

African (AFR) AF: 0.262 AC: 10865 AN: 41530

American (AMR) AF: 0.114 AC: 1742 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3468

East Asian (EAS) AF: 0.131 AC: 677 AN: 5170

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1192 AN: 10600

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8075 AN: 68006

Other (OTH) AF: 0.131 AC: 278 AN: 2116

Alfa AF: 0.124 Hom.: 2456

Bravo AF: 0.162

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.035
DANN	Benign	0.71
PhyloP100		-4.7
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: rs2274511; hg19: chr14-33829320;