rs6493791

Variant names:

• chr15-55488528-A-G
• rs6493791
• NM_130810.4:c.405+2595T>C

Variant summary

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

The NM_130810.4(DNAAF4):​c.405+2595T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,032 control chromosomes in the GnomAD database, including 22,769 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 0.53 (22769 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664
• Publications: 2 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]

ENSG00000295638 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.405+2595T>C		intron_variant	Intron 4 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.405+2595T>C		intron_variant	Intron 4 of 8		NP_001028732.1
DNAAF4	NM_001033559.3	c.405+2595T>C		intron_variant	Intron 4 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.660+2595T>C		intron_variant	Intron 3 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.405+2595T>C		intron_variant	Intron 4 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80327 AN: 151914 Hom.: 22730 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.529 AC: 80413 AN: 152032 Hom.: 22769 Cov.: 32 AF XY: 0.523 AC XY: 38837 AN XY: 74314

African (AFR) AF: 0.735 AC: 30491 AN: 41466

American (AMR) AF: 0.377 AC: 5763 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3468

East Asian (EAS) AF: 0.259 AC: 1342 AN: 5176

South Asian (SAS) AF: 0.460 AC: 2218 AN: 4824

European-Finnish (FIN) AF: 0.432 AC: 4557 AN: 10552

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32922 AN: 67960

Other (OTH) AF: 0.492 AC: 1037 AN: 2106

Alfa AF: 0.498 Hom.: 54462

Bravo AF: 0.529

Asia WGS AF: 0.377 AC: 1308 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.27
PhyloP100		-0.66
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: rs6493791; hg19: chr15-55780726;