rs8034029

Variant names:

• chr15-55420659-C-T
• rs8034029
• ENST00000448430.6:c.1048-2526G>A

Variant summary

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

The ENST00000448430.6(DNAAF4):​c.1048-2526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,044 control chromosomes in the GnomAD database, including 4,156 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 0.18 (4156 hom., cov: 32)
• Consequence: DNAAF4 ENST00000448430.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• 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=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_001033560.2	c.1048-2526G>A		intron_variant	Intron 8 of 8		NP_001028732.1
DNAAF4-CCPG1	NR_037923.1	n.1408+11838G>A		intron_variant	Intron 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000448430.6	c.1048-2526G>A		intron_variant	Intron 7 of 7	1		ENSP00000403412.2
DNAAF4	ENST00000524160.5	n.*481-9504G>A		intron_variant	Intron 7 of 8	2		ENSP00000428097.1
DNAAF4-CCPG1	ENST00000565113.5	n.1184+11838G>A		intron_variant	Intron 8 of 15	2
DNAAF4-CCPG1	ENST00000568310.1	n.905+18813G>A		intron_variant	Intron 6 of 9	2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27023 AN: 151926 Hom.: 4150 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.178 AC: 27064 AN: 152044 Hom.: 4156 Cov.: 32 AF XY: 0.175 AC XY: 13007 AN XY: 74320

African (AFR) AF: 0.419 AC: 17368 AN: 41436

American (AMR) AF: 0.101 AC: 1546 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5182

South Asian (SAS) AF: 0.115 AC: 553 AN: 4828

European-Finnish (FIN) AF: 0.0857 AC: 906 AN: 10572

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0862 AC: 5858 AN: 67994

Other (OTH) AF: 0.148 AC: 312 AN: 2106

Alfa AF: 0.147 Hom.: 394

Bravo AF: 0.187

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.46
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: rs8034029; hg19: chr15-55712857;