rs6493791

Positions:

• chr15-55488528-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• 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/exons	MANE	UniProt
DNAAF4	NM_130810.4	c.405+2595T>C		intron_variant		ENST00000321149.7
DNAAF4-CCPG1	NR_037923.1	n.660+2595T>C		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033559.3	c.405+2595T>C		intron_variant
DNAAF4	NM_001033560.2	c.405+2595T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF4	ENST00000321149.7	c.405+2595T>C		intron_variant		1	NM_130810.4	P1

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

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.492

Alfa AF: 0.484 Hom.: 30427

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6493791; hg19: chr15-55780726;