NM_001164749.2:c.51-35739A>G

Variant names:

• chr14-33020166-A-G
• rs17455703
• NM_001164749.2:c.51-35739A>G

Variant summary

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

The NM_001164749.2(NPAS3):​c.51-35739A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,194 control chromosomes in the GnomAD database, including 4,535 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 0.24 (4535 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698
• 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 (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164749.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	NM_001164749.2	MANE Select	c.51-35739A>G		intron	N/A	NP_001158221.1	X5D2Q4
	NPAS3	NM_173159.3		c.50+80800A>G		intron	N/A	NP_775182.1	Q8IXF0-3
	NPAS3	NM_001394988.1		c.50+80800A>G		intron	N/A	NP_001381917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS3	ENST00000356141.9	TSL:1 MANE Select	c.51-35739A>G		intron	N/A	ENSP00000348460.4	Q8IXF0-1
	NPAS3	ENST00000357798.9	TSL:1	c.50+80800A>G		intron	N/A	ENSP00000350446.5	Q8IXF0-3
	NPAS3	ENST00000548645.5	TSL:1	c.50+80800A>G		intron	N/A	ENSP00000448916.1	Q8IXF0-2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36731 AN: 152074 Hom.: 4538 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.241 AC: 36734 AN: 152194 Hom.: 4535 Cov.: 33 AF XY: 0.241 AC XY: 17938 AN XY: 74398

African (AFR) AF: 0.211 AC: 8761 AN: 41524

American (AMR) AF: 0.225 AC: 3446 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3472

East Asian (EAS) AF: 0.181 AC: 936 AN: 5182

South Asian (SAS) AF: 0.335 AC: 1613 AN: 4822

European-Finnish (FIN) AF: 0.246 AC: 2603 AN: 10588

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17875 AN: 67988

Other (OTH) AF: 0.236 AC: 499 AN: 2112

Alfa AF: 0.248 Hom.: 2732

Bravo AF: 0.237

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		0.70
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: rs17455703; hg19: chr14-33489372;