rs3754675

Variant names:

• chr2-100933381-T-C
• rs3754675
• NM_002518.4:c.273+380T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002518.4(NPAS2):​c.273+380T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,262 control chromosomes in the GnomAD database, including 1,932 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 (1932 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.909
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.273+380T>C		intron_variant	Intron 4 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.273+380T>C		intron_variant	Intron 4 of 20	1	NM_002518.4	ENSP00000338283.5

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18107 AN: 152144 Hom.: 1916 Cov.: 32

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.119 AC: 18144 AN: 152262 Hom.: 1932 Cov.: 32 AF XY: 0.128 AC XY: 9527 AN XY: 74444

African (AFR) AF: 0.0492 AC: 2045 AN: 41578

American (AMR) AF: 0.322 AC: 4919 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1781 AN: 5180

South Asian (SAS) AF: 0.204 AC: 986 AN: 4832

European-Finnish (FIN) AF: 0.165 AC: 1752 AN: 10588

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0871 AC: 5922 AN: 68016

Other (OTH) AF: 0.126 AC: 267 AN: 2114

Alfa AF: 0.102 Hom.: 2404

Bravo AF: 0.130

Asia WGS AF: 0.292 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.62
PhyloP100		-0.91
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: rs3754675; hg19: chr2-101549843;