rs8004607

Variant names:

• chr14-33636319-G-C
• rs8004607
• NM_001164749.2:c.559-39892G>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.559-39892G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,214 control chromosomes in the GnomAD database, including 4,259 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 0.19 (4259 hom., cov: 33)
• Consequence: NPAS3 NM_001164749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• 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]

LOC124903300 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS3	NM_001164749.2	c.559-39892G>C		intron_variant	Intron 5 of 11	ENST00000356141.9	NP_001158221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS3	ENST00000356141.9	c.559-39892G>C		intron_variant	Intron 5 of 11	1	NM_001164749.2	ENSP00000348460.4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29266 AN: 152096 Hom.: 4242 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.193 AC: 29329 AN: 152214 Hom.: 4259 Cov.: 33 AF XY: 0.189 AC XY: 14037 AN XY: 74436

African (AFR) AF: 0.413 AC: 17125 AN: 41474

American (AMR) AF: 0.134 AC: 2043 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.127 AC: 660 AN: 5184

South Asian (SAS) AF: 0.127 AC: 612 AN: 4830

European-Finnish (FIN) AF: 0.0843 AC: 895 AN: 10612

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7206 AN: 68020

Other (OTH) AF: 0.161 AC: 340 AN: 2116

Alfa AF: 0.150 Hom.: 332

Bravo AF: 0.205

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.79
DANN	Benign	0.36
PhyloP100		-0.18
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: rs8004607; hg19: chr14-34105525;