rs1811399

Variant names:

• chr2-100862552-C-A
• rs1811399
• NM_002518.4:c.-23+42138C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-100862552-C-A
• chr2-100862552-C-T

Variant summary

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

The NM_002518.4(NPAS2):​c.-23+42138C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,044 control chromosomes in the GnomAD database, including 40,030 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 0.72 (40030 hom., cov: 31)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 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.-23+42138C>A		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.-23+42138C>A		intron	N/A	ENSP00000338283.5	Q99743
	NPAS2	ENST00000906777.1		c.-140-36697C>A		intron	N/A	ENSP00000576836.1
	NPAS2	ENST00000906778.1		c.-23+41968C>A		intron	N/A	ENSP00000576837.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109965 AN: 151928 Hom.: 40001 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.724 AC: 110050 AN: 152044 Hom.: 40030 Cov.: 31 AF XY: 0.725 AC XY: 53865 AN XY: 74346

African (AFR) AF: 0.675 AC: 27984 AN: 41442

American (AMR) AF: 0.649 AC: 9914 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2371 AN: 3470

East Asian (EAS) AF: 0.686 AC: 3542 AN: 5160

South Asian (SAS) AF: 0.739 AC: 3570 AN: 4828

European-Finnish (FIN) AF: 0.808 AC: 8546 AN: 10574

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51691 AN: 67974

Other (OTH) AF: 0.720 AC: 1518 AN: 2108

Alfa AF: 0.741 Hom.: 176603

Bravo AF: 0.707

Asia WGS AF: 0.689 AC: 2397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.46
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: rs1811399; hg19: chr2-101479014;