rs8040756

Positions:

• chr15-55506401-G-A
• chr15-55506401-G-T

Variant summary

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

The NM_130810.4(DNAAF4):​c.-256+1721C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,026 control chromosomes in the GnomAD database, including 9,573 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 0.28 (9573 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.-256+1721C>T		intron_variant		ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.-256+1721C>T		intron_variant			NP_001028732.1
DNAAF4	NM_001033559.3	c.-256+1721C>T		intron_variant			NP_001028731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.-256+1721C>T		intron_variant		1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43017 AN: 151906 Hom.: 9536 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.284 AC: 43111 AN: 152026 Hom.: 9573 Cov.: 32 AF XY: 0.279 AC XY: 20732 AN XY: 74290

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.234

Alfa AF: 0.180 Hom.: 1856

Bravo AF: 0.298

Asia WGS AF: 0.250 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8040756; hg19: chr15-55798599;