rs12594039

Variant names:

• chr15-55422328-T-C
• rs12594039
• ENST00000448430.6:c.1048-4195A>G

Variant summary

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

The ENST00000448430.6(DNAAF4):​c.1048-4195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 152,204 control chromosomes in the GnomAD database, including 270 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 0.050 (270 hom., cov: 32)
• Consequence: DNAAF4 ENST00000448430.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_001033560.2	c.1048-4195A>G		intron_variant	Intron 8 of 8		NP_001028732.1
DNAAF4-CCPG1	NR_037923.1	n.1408+10169A>G		intron_variant	Intron 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000448430.6	c.1048-4195A>G		intron_variant	Intron 7 of 7	1		ENSP00000403412.2
DNAAF4	ENST00000524160.5	n.*480+10169A>G		intron_variant	Intron 7 of 8	2		ENSP00000428097.1
DNAAF4-CCPG1	ENST00000565113.5	n.1184+10169A>G		intron_variant	Intron 8 of 15	2
DNAAF4-CCPG1	ENST00000568310.1	n.905+17144A>G		intron_variant	Intron 6 of 9	2

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7555 AN: 152086 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0551

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0496 AC: 7550 AN: 152204 Hom.: 270 Cov.: 32 AF XY: 0.0493 AC XY: 3668 AN XY: 74414

African (AFR) AF: 0.0167 AC: 692 AN: 41534

American (AMR) AF: 0.0480 AC: 733 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 222 AN: 3472

East Asian (EAS) AF: 0.156 AC: 805 AN: 5164

South Asian (SAS) AF: 0.112 AC: 538 AN: 4822

European-Finnish (FIN) AF: 0.0339 AC: 359 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4014 AN: 68016

Other (OTH) AF: 0.0549 AC: 116 AN: 2112

Alfa AF: 0.0483 Hom.: 36

Bravo AF: 0.0484

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.58
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12594039; hg19: chr15-55714526;