19-47026483-T-C

Position:

• chr19-47026483-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NPAS1	NM_002517.4	c.358+4636T>C		intron_variant		ENST00000602212.6	NP_002508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS1	ENST00000602212.6	c.358+4636T>C		intron_variant		1	NM_002517.4	ENSP00000469142.1
NPAS1	ENST00000449844.6	c.358+4636T>C		intron_variant		1		ENSP00000405290.1
NPAS1	ENST00000602189.5	c.-170-5795T>C		intron_variant		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

Gnomad4 AFR AF: 0.0870

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.302

Alfa AF: 0.327 Hom.: 5967

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1477340; hg19: chr19-47529740;