chr19-47026483-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002517.4(NPAS1):​c.358+4636T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS1	NM_002517.4	MANE Select	c.358+4636T>A		intron	N/A	NP_002508.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS1	ENST00000602212.6	TSL:1 MANE Select	c.358+4636T>A		intron	N/A	ENSP00000469142.1
	NPAS1	ENST00000449844.6	TSL:1	c.358+4636T>A		intron	N/A	ENSP00000405290.1
	NPAS1	ENST00000602189.5	TSL:5	c.-170-5795T>A		intron	N/A	ENSP00000472679.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.68
PhyloP100		-0.033

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;