rs1542178

Variant names:

• chr2-100979013-A-G
• rs1542178
• NM_002518.4:c.1482+1214A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-100979013-A-G
• chr2-100979013-A-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.1482+1214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,134 control chromosomes in the GnomAD database, including 42,984 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 0.74 (42984 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.69
• Publications: 9 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.1482+1214A>G		intron_variant	Intron 15 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.1482+1214A>G		intron_variant	Intron 15 of 20	1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000474550.5	n.816+1214A>G		intron_variant	Intron 4 of 8	1
NPAS2	ENST00000450763.1	c.279+1214A>G		intron_variant	Intron 3 of 4	4		ENSP00000392125.1
NPAS2	ENST00000471974.1	n.342+1214A>G		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113104 AN: 152016 Hom.: 42934 Cov.: 33

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.744 AC: 113211 AN: 152134 Hom.: 42984 Cov.: 33 AF XY: 0.748 AC XY: 55653 AN XY: 74370

African (AFR) AF: 0.897 AC: 37259 AN: 41526

American (AMR) AF: 0.729 AC: 11143 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2285 AN: 3472

East Asian (EAS) AF: 0.822 AC: 4254 AN: 5174

South Asian (SAS) AF: 0.731 AC: 3526 AN: 4822

European-Finnish (FIN) AF: 0.737 AC: 7794 AN: 10578

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44487 AN: 67970

Other (OTH) AF: 0.730 AC: 1541 AN: 2110

Alfa AF: 0.686 Hom.: 62207

Bravo AF: 0.751

Asia WGS AF: 0.797 AC: 2771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.016
DANN	Benign	0.38
PhyloP100		-5.7
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: rs1542178; hg19: chr2-101595475;