15-55477773-T-C

Variant summary

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

The NM_130810.4(DNAAF4):c.406-10612A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,566 control chromosomes in the GnomAD database, including 20,629 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 (20629 hom., cov: 29)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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 (EAS) 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.406-10612A>G		intron_variant		ENST00000321149.7
DNAAF4-CCPG1	NR_037923.1	n.661-10612A>G		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033559.3	c.406-10612A>G		intron_variant
DNAAF4	NM_001033560.2	c.406-10612A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF4	ENST00000321149.7	c.406-10612A>G		intron_variant		1	NM_130810.4	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76069 AN: 151452 Hom.: 20618 Cov.: 29

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.502 AC: 76101 AN: 151566 Hom.: 20629 Cov.: 29 AF XY: 0.507 AC XY: 37537 AN XY: 74028

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.539

Alfa AF: 0.511 Hom.: 2505

Bravo AF: 0.503

Asia WGS AF: 0.637 AC: 2216 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	1.8
Dann	Benign	0.33

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: rs4144134; hg19: chr15-55769971;