rs1111533

Variant names:

• chr14-33321403-A-C
• rs1111533
• NM_001164749.2:c.386-45783A>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.386-45783A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,974 control chromosomes in the GnomAD database, including 1,510 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 0.12 (1510 hom., cov: 32)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.386-45783A>C		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.386-45783A>C		intron_variant	Intron 3 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17835 AN: 151856 Hom.: 1502 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0942

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0638

Gnomad OTH AF: 0.0947

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

GnomAD4 genome AF: 0.118 AC: 17872 AN: 151974 Hom.: 1510 Cov.: 32 AF XY: 0.120 AC XY: 8895 AN XY: 74294

African (AFR) AF: 0.217 AC: 8980 AN: 41414

American (AMR) AF: 0.0600 AC: 917 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1726 AN: 5126

South Asian (SAS) AF: 0.100 AC: 483 AN: 4810

European-Finnish (FIN) AF: 0.0942 AC: 995 AN: 10564

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0638 AC: 4337 AN: 68000

Other (OTH) AF: 0.0956 AC: 202 AN: 2112

Alfa AF: 0.0731 Hom.: 914

Bravo AF: 0.121

Asia WGS AF: 0.225 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.66
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: rs1111533; hg19: chr14-33790609;