rs12324434

Positions:

• chr15-55422237-T-C
• chr15-55422237-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448430.6(DNAAF4):​c.1048-4104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,738 control chromosomes in the GnomAD database, including 13,406 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 0.40 (13406 hom., cov: 31)
• Consequence: DNAAF4 ENST00000448430.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4-CCPG1	NR_037923.1	n.1408+10260A>G		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033560.2	c.1048-4104A>G		intron_variant			NP_001028732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000448430.6	c.1048-4104A>G		intron_variant		1		ENSP00000403412
DNAAF4	ENST00000524160.5	c.*480+10260A>G		intron_variant, NMD_transcript_variant		2		ENSP00000428097

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60700 AN: 151620 Hom.: 13395 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.400 AC: 60729 AN: 151738 Hom.: 13406 Cov.: 31 AF XY: 0.411 AC XY: 30432 AN XY: 74130

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.428

Alfa AF: 0.407 Hom.: 9089

Bravo AF: 0.403

Asia WGS AF: 0.611 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.8
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12324434; hg19: chr15-55714435;