15-55478713-C-T

Variant names:

• chr15-55478713-C-T
• rs685935
• NM_130810.4:c.406-11552G>A

Variant summary

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

The NM_130810.4(DNAAF4):​c.406-11552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,968 control chromosomes in the GnomAD database, including 20,440 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 0.50 (20440 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.62
• Publications: 12 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.406-11552G>A		intron_variant	Intron 4 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.406-11552G>A		intron_variant	Intron 4 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.406-11552G>A		intron_variant	Intron 4 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.661-11552G>A		intron_variant	Intron 3 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.406-11552G>A		intron_variant	Intron 4 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75745 AN: 151850 Hom.: 20428 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.499 AC: 75775 AN: 151968 Hom.: 20440 Cov.: 32 AF XY: 0.504 AC XY: 37405 AN XY: 74248

African (AFR) AF: 0.283 AC: 11736 AN: 41432

American (AMR) AF: 0.648 AC: 9895 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2074 AN: 3470

East Asian (EAS) AF: 0.742 AC: 3834 AN: 5170

South Asian (SAS) AF: 0.556 AC: 2679 AN: 4816

European-Finnish (FIN) AF: 0.579 AC: 6116 AN: 10556

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37660 AN: 67948

Other (OTH) AF: 0.537 AC: 1134 AN: 2112

Alfa AF: 0.537 Hom.: 18930

Bravo AF: 0.499

Asia WGS AF: 0.632 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.49
PhyloP100		-4.6
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: rs685935; hg19: chr15-55770911;