rs3759864

chr15-55430015-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DNAAF4-CCPG1	NR_037923.1	n.1408+2482A>G		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033560.2	c.1047+4890A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF4	ENST00000448430.6	c.1047+4890A>G		intron_variant		1
DNAAF4	ENST00000524160.5	c.*480+2482A>G		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0477

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0337

Gnomad4 NFE AF: 0.0588

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0575 Hom.: 141

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3759864; hg19: chr15-55722213;