rs1542178

chr2-100979013-A-Gchr2-100979013-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
NPAS2	NM_002518.4	c.1482+1214A>G		intron_variant		ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.1482+1214A>G		intron_variant		1	NM_002518.4	P1
NPAS2	ENST00000474550.5	n.816+1214A>G		intron_variant, non_coding_transcript_variant		1
NPAS2	ENST00000450763.1	c.279+1214A>G		intron_variant		4
NPAS2	ENST00000471974.1	n.342+1214A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.730

Alfa AF: 0.680 Hom.: 48185

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

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: rs1542178; hg19: chr2-101595475;