chr15-55427489-T-A

Variant names:

• chr15-55427489-T-A
• rs7174102
• ENST00000448430.6:c.1047+7416A>T

Variant summary

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

The ENST00000448430.6(DNAAF4):​c.1047+7416A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,036 control chromosomes in the GnomAD database, including 6,055 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 0.25 (6055 hom., cov: 31)
• Consequence: DNAAF4 ENST00000448430.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448430.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	NM_001033560.2		c.1047+7416A>T		intron	N/A	NP_001028732.1
	DNAAF4-CCPG1	NR_037923.1		n.1408+5008A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	ENST00000448430.6	TSL:1	c.1047+7416A>T		intron	N/A	ENSP00000403412.2
	DNAAF4	ENST00000524160.5	TSL:2	n.*480+5008A>T		intron	N/A	ENSP00000428097.1
	DNAAF4-CCPG1	ENST00000565113.5	TSL:2	n.1184+5008A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38171 AN: 151918 Hom.: 6058 Cov.: 31

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0691

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.251 AC: 38159 AN: 152036 Hom.: 6055 Cov.: 31 AF XY: 0.249 AC XY: 18514 AN XY: 74314

African (AFR) AF: 0.0868 AC: 3606 AN: 41536

American (AMR) AF: 0.214 AC: 3270 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3470

East Asian (EAS) AF: 0.0693 AC: 359 AN: 5182

South Asian (SAS) AF: 0.202 AC: 970 AN: 4808

European-Finnish (FIN) AF: 0.352 AC: 3716 AN: 10542

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24206 AN: 67934

Other (OTH) AF: 0.265 AC: 559 AN: 2106

Alfa AF: 0.195 Hom.: 516

Bravo AF: 0.234

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.46
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7174102; hg19: chr15-55719687;