rs1811399

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.-23+42138C>A		intron_variant		ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.-23+42138C>A		intron_variant		1	NM_002518.4	ENSP00000338283	P1
NPAS2	ENST00000427413.5	c.173+41353C>A		intron_variant		3		ENSP00000397595

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

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.720

Alfa AF: 0.744 Hom.: 83342

Bravo AF: 0.707

Asia WGS AF: 0.689 AC: 2397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1811399; hg19: chr2-101479014;