ENST00000474550.5:n.1462T>A

Variant names:

• chr2-100982876-T-A
• rs6543004
• ENST00000474550.5:n.1462T>A

Variant summary

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

The ENST00000474550.5(NPAS2):​n.1462T>A variant causes a non coding transcript exon 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 ENST00000474550.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 1 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=-0.9).
• 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 rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.1629+499T>A		intron_variant	Intron 16 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.1629+499T>A		intron_variant	Intron 16 of 20	1	NM_002518.4	ENSP00000338283.5

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

African (AFR) AF: 0.0500 AC: 1 AN: 20

American (AMR) AF: 0.114 AC: 8 AN: 70

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18

East Asian (EAS) AF: 0.00 AC: 0 AN: 18

South Asian (SAS) AF: 0.0667 AC: 2 AN: 30

European-Finnish (FIN) AF: 0.233 AC: 7 AN: 30

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.150 AC: 106 AN: 706

Other (OTH) AF: 0.158 AC: 6 AN: 38

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

African (AFR) AF: 0.123 AC: 5120 AN: 41532

American (AMR) AF: 0.104 AC: 1596 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 193 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0636 AC: 307 AN: 4824

European-Finnish (FIN) AF: 0.154 AC: 1638 AN: 10602

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8976 AN: 68006

Other (OTH) AF: 0.117 AC: 246 AN: 2106

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
PhyloP100		-0.44
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: rs6543004; hg19: chr2-101599338;