19-47026483-T-C

Variant names:

• chr19-47026483-T-C
• rs1477340
• NM_002517.4:c.358+4636T>C

Variant summary

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

The NM_002517.4(NPAS1):​c.358+4636T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,058 control chromosomes in the GnomAD database, including 7,090 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 (7090 hom., cov: 32)
• Consequence: NPAS1 NM_002517.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS1	NM_002517.4	c.358+4636T>C		intron_variant	Intron 3 of 11	ENST00000602212.6	NP_002508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS1	ENST00000602212.6	c.358+4636T>C		intron_variant	Intron 3 of 11	1	NM_002517.4	ENSP00000469142.1
NPAS1	ENST00000449844.6	c.358+4636T>C		intron_variant	Intron 2 of 10	1		ENSP00000405290.1
NPAS1	ENST00000602189.5	c.-170-5795T>C		intron_variant	Intron 1 of 9	5		ENSP00000472679.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42378 AN: 151942 Hom.: 7078 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.279 AC: 42407 AN: 152058 Hom.: 7090 Cov.: 32 AF XY: 0.286 AC XY: 21235 AN XY: 74322

African (AFR) AF: 0.0870 AC: 3611 AN: 41484

American (AMR) AF: 0.328 AC: 5012 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1535 AN: 3470

East Asian (EAS) AF: 0.387 AC: 1996 AN: 5158

South Asian (SAS) AF: 0.507 AC: 2448 AN: 4824

European-Finnish (FIN) AF: 0.354 AC: 3738 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 23003 AN: 67970

Other (OTH) AF: 0.302 AC: 640 AN: 2116

Alfa AF: 0.322 Hom.: 10894

Bravo AF: 0.263

Asia WGS AF: 0.431 AC: 1494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.66
PhyloP100		-0.033
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: rs1477340; hg19: chr19-47529740;