rs1369481

Variant names:

• chr2-100895497-T-C
• rs1369481
• NM_002518.4:c.-22-9236T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-100895497-T-C
• chr2-100895497-T-G

Variant summary

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

The NM_002518.4(NPAS2):​c.-22-9236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,182 control chromosomes in the GnomAD database, including 45,794 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 0.77 (45794 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484
• Publications: 27 publications found

Genes affected

NPAS2 (HGNC:7895): (neuronal PAS domain protein 2) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. A similar mouse protein may play a regulatory role in the acquisition of specific types of memory. It also may function as a part of a molecular clock operative in the mammalian forebrain. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002518.4. 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
	NPAS2	NM_002518.4	MANE Select	c.-22-9236T>C		intron	N/A	NP_002509.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.-22-9236T>C		intron	N/A	ENSP00000338283.5	Q99743
	NPAS2	ENST00000906777.1		c.-140-3752T>C		intron	N/A	ENSP00000576836.1
	NPAS2	ENST00000906778.1		c.-22-9236T>C		intron	N/A	ENSP00000576837.1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117201 AN: 152062 Hom.: 45742 Cov.: 33

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.771 AC: 117304 AN: 152182 Hom.: 45794 Cov.: 33 AF XY: 0.775 AC XY: 57647 AN XY: 74388

African (AFR) AF: 0.898 AC: 37327 AN: 41546

American (AMR) AF: 0.654 AC: 10003 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2411 AN: 3466

East Asian (EAS) AF: 0.751 AC: 3873 AN: 5156

South Asian (SAS) AF: 0.797 AC: 3845 AN: 4822

European-Finnish (FIN) AF: 0.829 AC: 8787 AN: 10604

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48588 AN: 67990

Other (OTH) AF: 0.745 AC: 1575 AN: 2114

Alfa AF: 0.725 Hom.: 27056

Bravo AF: 0.760

Asia WGS AF: 0.781 AC: 2717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.63
PhyloP100		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs1369481; hg19: chr2-101511959;