rs6543004

chr2-100982876-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002518.4(NPAS2):c.1629+499T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 153,146 control chromosomes in the GnomAD database, including 1,167 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 0.12 (1155 hom., cov: 34)
  • Exomes 𝑓: 0.14 (12 hom.)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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 = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4	c.1629+499T>A		intron_variant		ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.1629+499T>A		intron_variant		1	NM_002518.4	P1
NPAS2	ENST00000474550.5	n.1462T>A		non_coding_transcript_exon_variant	5/9	1
NPAS2	ENST00000433408.1	c.124+499T>A		intron_variant		5
NPAS2	ENST00000450763.1	c.426+499T>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18208 AN: 152094 Hom.: 1154 Cov.: 34

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.139 AC: 130 AN: 934 Hom.: 12 Cov.: 0 AF XY: 0.132 AC XY: 64 AN XY: 484

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0667

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.120 AC: 18218 AN: 152212 Hom.: 1155 Cov.: 34 AF XY: 0.120 AC XY: 8917 AN XY: 74430

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0557

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.117

Alfa AF: 0.120 Hom.: 134

Bravo AF: 0.118

Asia WGS AF: 0.0330 AC: 119 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	3.4
Dann	Benign	0.66

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: rs6543004; hg19: chr2-101599338;