NM_002518.4:c.1482+974A>G

Variant names:

• chr2-100978773-A-G
• rs1542179
• NM_002518.4:c.1482+974A>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.1482+974A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,074 control chromosomes in the GnomAD database, including 13,499 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 0.40 (13499 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 17 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	NM_002518.4	MANE Select	c.1482+974A>G		intron	N/A	NP_002509.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.1482+974A>G		intron	N/A	ENSP00000338283.5
	NPAS2	ENST00000474550.5	TSL:1	n.816+974A>G		intron	N/A
	NPAS2	ENST00000450763.1	TSL:4	c.279+974A>G		intron	N/A	ENSP00000392125.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60494 AN: 151956 Hom.: 13470 Cov.: 33

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.398 AC: 60585 AN: 152074 Hom.: 13499 Cov.: 33 AF XY: 0.407 AC XY: 30287 AN XY: 74364

African (AFR) AF: 0.541 AC: 22423 AN: 41472

American (AMR) AF: 0.408 AC: 6227 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3470

East Asian (EAS) AF: 0.757 AC: 3917 AN: 5172

South Asian (SAS) AF: 0.486 AC: 2342 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4561 AN: 10578

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19307 AN: 67972

Other (OTH) AF: 0.353 AC: 745 AN: 2110

Alfa AF: 0.329 Hom.: 5216

Bravo AF: 0.400

Asia WGS AF: 0.628 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		-0.69
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: rs1542179; hg19: chr2-101595235; COSMIC: COSV59559714; COSMIC: COSV59559714;