rs7935572

Variant names:

• chr11-66416452-G-A
• rs7935572
• ENST00000526186.3:n.1101-341G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000526186.3(ENSG00000254510):​n.1101-341G>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: ENSG00000254510 ENST00000526186.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 8 publications found

Genes affected

ENSG00000254510 (HGNC:):

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]

NPAS4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526186.3. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000254510	ENST00000526186.3	TSL:2	n.1101-341G>A		intron	N/A
	ENSG00000254510	ENST00000533759.2	TSL:5	n.614-341G>A		intron	N/A
	ENSG00000254510	ENST00000658173.2		n.1011-341G>A		intron	N/A

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

African (AFR) AF: 0.227 AC: 9429 AN: 41492

American (AMR) AF: 0.0568 AC: 869 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0688 AC: 239 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0387 AC: 187 AN: 4834

European-Finnish (FIN) AF: 0.0484 AC: 514 AN: 10614

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0588 AC: 4001 AN: 68032

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.0814 Hom.: 195

Bravo AF: 0.108

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs7935572; hg19: chr11-66183923;