rs3759864

Variant names:

• chr15-55430015-T-C
• rs3759864
• ENST00000448430.6:c.1047+4890A>G

Variant summary

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

The ENST00000448430.6(DNAAF4):​c.1047+4890A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152,182 control chromosomes in the GnomAD database, including 269 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 0.049 (269 hom., cov: 32)
• Consequence: DNAAF4 ENST00000448430.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_001033560.2	c.1047+4890A>G		intron_variant	Intron 8 of 8		NP_001028732.1
DNAAF4-CCPG1	NR_037923.1	n.1408+2482A>G		intron_variant	Intron 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000448430.6	c.1047+4890A>G		intron_variant	Intron 7 of 7	1		ENSP00000403412.2
DNAAF4	ENST00000524160.5	n.*480+2482A>G		intron_variant	Intron 7 of 8	2		ENSP00000428097.1
DNAAF4-CCPG1	ENST00000565113.5	n.1184+2482A>G		intron_variant	Intron 8 of 15	2
DNAAF4-CCPG1	ENST00000568310.1	n.905+9457A>G		intron_variant	Intron 6 of 9	2

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7517 AN: 152064 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0588

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0494 AC: 7515 AN: 152182 Hom.: 269 Cov.: 32 AF XY: 0.0492 AC XY: 3661 AN XY: 74418

African (AFR) AF: 0.0159 AC: 659 AN: 41526

American (AMR) AF: 0.0477 AC: 727 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3470

East Asian (EAS) AF: 0.171 AC: 882 AN: 5170

South Asian (SAS) AF: 0.101 AC: 488 AN: 4822

European-Finnish (FIN) AF: 0.0337 AC: 358 AN: 10614

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0588 AC: 3998 AN: 68008

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0574 Hom.: 156

Bravo AF: 0.0486

Asia WGS AF: 0.118 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.70
PhyloP100		0.67
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: rs3759864; hg19: chr15-55722213;