rs11123857

chr2-100987350-A-G

Variant summary

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

The NM_002518.4(NPAS2):c.1630-729A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,268 control chromosomes in the GnomAD database, including 6,459 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 0.28 (6459 hom., cov: 34)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4	c.1630-729A>G		intron_variant		ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.1630-729A>G		intron_variant		1	NM_002518.4	P1
NPAS2	ENST00000474550.5	n.5936A>G		non_coding_transcript_exon_variant	5/9	1
NPAS2	ENST00000433408.1	c.125-729A>G		intron_variant		5
NPAS2	ENST00000450763.1	c.426+4973A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42219 AN: 152142 Hom.: 6445 Cov.: 34

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00730

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.278 AC: 42269 AN: 152260 Hom.: 6459 Cov.: 34 AF XY: 0.274 AC XY: 20375 AN XY: 74456

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.00732

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.244

Alfa AF: 0.269 Hom.: 6889

Bravo AF: 0.272

Asia WGS AF: 0.0910 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.035
Dann	Benign	0.40

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: rs11123857; hg19: chr2-101603812;