rs12594039

Positions:

• chr15-55422328-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	Protein	UniProt
DNAAF4-CCPG1	NR_037923.1	n.1408+10169A>G		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033560.2	c.1048-4195A>G		intron_variant			NP_001028732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000448430.6	c.1048-4195A>G		intron_variant		1		ENSP00000403412
DNAAF4	ENST00000524160.5	c.*480+10169A>G		intron_variant, NMD_transcript_variant		2		ENSP00000428097

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

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0480

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0490 Hom.: 35

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12594039; hg19: chr15-55714526;