rs8043049

Variant names:

• chr15-55485590-T-C
• rs8043049
• NM_130810.4:c.405+5533A>G

Variant summary

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

The NM_130810.4(DNAAF4):​c.405+5533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,944 control chromosomes in the GnomAD database, including 6,711 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 0.29 (6711 hom., cov: 31)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.405+5533A>G		intron_variant	Intron 4 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.405+5533A>G		intron_variant	Intron 4 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.405+5533A>G		intron_variant	Intron 4 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.660+5533A>G		intron_variant	Intron 3 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.405+5533A>G		intron_variant	Intron 4 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43438 AN: 151824 Hom.: 6714 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0665

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.286 AC: 43446 AN: 151944 Hom.: 6711 Cov.: 31 AF XY: 0.282 AC XY: 20968 AN XY: 74248

African (AFR) AF: 0.232 AC: 9606 AN: 41434

American (AMR) AF: 0.223 AC: 3405 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3470

East Asian (EAS) AF: 0.0667 AC: 345 AN: 5176

South Asian (SAS) AF: 0.207 AC: 995 AN: 4810

European-Finnish (FIN) AF: 0.322 AC: 3385 AN: 10526

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23842 AN: 67946

Other (OTH) AF: 0.273 AC: 578 AN: 2114

Alfa AF: 0.328 Hom.: 8359

Bravo AF: 0.276

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.60
PhyloP100		-0.16
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: rs8043049; hg19: chr15-55777788;