rs201134548

Variant names:

• chr19-47036007-G-C
• rs201134548
• NM_002517.4:c.566G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-47036007-G-C
• chr19-47036007-G-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002517.4(NPAS1):​c.566G>C​(p.Gly189Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000475 in 1,582,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (0 hom.)
• Consequence: NPAS1 NM_002517.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41
• Publications: 0 publications found

Genes affected

NPAS1 (HGNC:7894): (neuronal PAS domain protein 1) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. Studies of a related mouse gene suggest that it functions in neurons. The exact function of this gene is unclear, but it may play protective or modulatory roles during late embryogenesis and postnatal development. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11660424).
• BS2: High AC in GnomAd4 at 23 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002517.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS1	NM_002517.4	MANE Select	c.566G>C	p.Gly189Ala	missense	Exon 6 of 12	NP_002508.2
	NPAS1	NM_001321086.2		c.38G>C	p.Gly13Ala	missense	Exon 2 of 8	NP_001308015.1	Q99742-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS1	ENST00000602212.6	TSL:1 MANE Select	c.566G>C	p.Gly189Ala	missense	Exon 6 of 12	ENSP00000469142.1	Q99742-1
	NPAS1	ENST00000449844.6	TSL:1	c.566G>C	p.Gly189Ala	missense	Exon 5 of 11	ENSP00000405290.1	Q99742-1
	NPAS1	ENST00000906441.1		c.566G>C	p.Gly189Ala	missense	Exon 6 of 12	ENSP00000576500.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152110 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000195 AC: 42 AN: 215350 AF XY: 0.000213

Gnomad AFR exome AF: 0.000272

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.000197

GnomAD4 exome AF: 0.000510 AC: 729 AN: 1429918 Hom.: 0 Cov.: 30 AF XY: 0.000463 AC XY: 329 AN XY: 710246

African (AFR) AF: 0.0000625 AC: 2 AN: 31988

American (AMR) AF: 0.00 AC: 0 AN: 38276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23862

East Asian (EAS) AF: 0.00 AC: 0 AN: 39164

South Asian (SAS) AF: 0.00 AC: 0 AN: 82218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.000648 AC: 711 AN: 1097970

Other (OTH) AF: 0.000272 AC: 16 AN: 58896

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152110 Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10 AN XY: 74304

African (AFR) AF: 0.0000966 AC: 4 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000154 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000206 AC: 25

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.064
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N
PhyloP100		4.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.10
Sift	Benign	0.64	T
Sift4G	Benign	0.90	T
Polyphen		0.38	B
Vest4		0.32
MVP		0.44
MPC		1.6
ClinPred		0.053	T
GERP RS		5.1
Varity_R		0.25
gMVP		0.24
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs201134548; hg19: chr19-47539265;