11-66416452-G-A

Position:

• chr11-66416452-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The XM_047426764.1(NPAS4):​c.54-4550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,252 control chromosomes in the GnomAD database, including 1,230 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 0.10 (1230 hom., cov: 32)
• Consequence: NPAS4 XM_047426764.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

Genes affected

NPAS4 (HGNC:18983): (neuronal PAS domain protein 4) NXF is a member of the basic helix-loop-helix-PER (MIM 602260)-ARNT (MIM 126110)-SIM (see SIM2; MIM 600892) (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008]

ENSG00000254510 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS4	XM_047426764.1	c.54-4550G>A		intron_variant			XP_047282720.1
NPAS4	XM_047426765.1	c.54-4550G>A		intron_variant			XP_047282721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000254510	ENST00000526186.2	n.1093-341G>A		intron_variant		2
ENSG00000254510	ENST00000533759.1	n.604-341G>A		intron_variant		5
ENSG00000254510	ENST00000658173.2	n.1011-341G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15480 AN: 152134 Hom.: 1231 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0588

Gnomad OTH AF: 0.0970

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

GnomAD4 genome AF: 0.102 AC: 15502 AN: 152252 Hom.: 1230 Cov.: 32 AF XY: 0.0986 AC XY: 7343 AN XY: 74444

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0387

Gnomad4 FIN AF: 0.0484

Gnomad4 NFE AF: 0.0588

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.0782 Hom.: 176

Bravo AF: 0.108

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7935572; hg19: chr11-66183923;