NM_130810.4:c.1047+598C>A

Variant names:

• chr15-55434307-G-T
• rs4774768
• NM_130810.4:c.1047+598C>A

Variant summary

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

The NM_130810.4(DNAAF4):​c.1047+598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 150,758 control chromosomes in the GnomAD database, including 16,650 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 0.45 (16650 hom., cov: 28)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643
• Publications: 7 publications found

Genes affected

DNAAF4 (HGNC:21493): (dynein axonemal assembly factor 4) This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.1047+598C>A		intron_variant	Intron 8 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.1047+598C>A		intron_variant	Intron 8 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.1047+598C>A		intron_variant	Intron 8 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.1302+598C>A		intron_variant	Intron 7 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.1047+598C>A		intron_variant	Intron 8 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68435 AN: 150640 Hom.: 16631 Cov.: 28

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.454 AC: 68487 AN: 150758 Hom.: 16650 Cov.: 28 AF XY: 0.463 AC XY: 34006 AN XY: 73510

African (AFR) AF: 0.293 AC: 12033 AN: 41098

American (AMR) AF: 0.606 AC: 9014 AN: 14866

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1931 AN: 3456

East Asian (EAS) AF: 0.743 AC: 3810 AN: 5128

South Asian (SAS) AF: 0.566 AC: 2720 AN: 4802

European-Finnish (FIN) AF: 0.534 AC: 5508 AN: 10318

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31867 AN: 67792

Other (OTH) AF: 0.495 AC: 1041 AN: 2102

Alfa AF: 0.444 Hom.: 2468

Bravo AF: 0.457

Asia WGS AF: 0.633 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.65
PhyloP100		0.64
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: rs4774768; hg19: chr15-55726505;