rs3739008

Positions:

• chr2-100996106-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002518.4(NPAS2):​c.*524C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.282 in 496,326 control chromosomes in the GnomAD database, including 21,721 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5483 hom., cov: 32)
  • Exomes 𝑓: 0.30 (16238 hom.)
• Consequence: NPAS2 NM_002518.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68

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]

ENSG00000223947 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.*524C>T		3_prime_UTR_variant	21/21	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.*524C>T		3_prime_UTR_variant	21/21	1	NM_002518.4	ENSP00000338283.5
ENSG00000223947	ENST00000452364.1	n.1152-97G>A		intron_variant		1
NPAS2	ENST00000495559.1	n.3118C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37716 AN: 151886 Hom.: 5486 Cov.: 32

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.296 AC: 102005 AN: 344322 Hom.: 16238 Cov.: 6 AF XY: 0.300 AC XY: 51148 AN XY: 170598

Gnomad4 AFR exome AF: 0.0749

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.248 AC: 37713 AN: 152004 Hom.: 5483 Cov.: 32 AF XY: 0.249 AC XY: 18466 AN XY: 74298

Gnomad4 AFR AF: 0.0903

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.271

Alfa AF: 0.310 Hom.: 10263

Bravo AF: 0.241

Asia WGS AF: 0.289 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	17
DANN	Benign	0.90

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: rs3739008; hg19: chr2-101612568;