15-55495583-C-T

Variant summary

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

The NM_130810.4(DNAAF4):c.271+2129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,108 control chromosomes in the GnomAD database, including 60,981 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 0.89 (60981 hom., cov: 30)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF4	NM_130810.4	c.271+2129G>A		intron_variant		ENST00000321149.7
DNAAF4-CCPG1	NR_037923.1	n.526+2129G>A		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033559.3	c.271+2129G>A		intron_variant
DNAAF4	NM_001033560.2	c.271+2129G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF4	ENST00000321149.7	c.271+2129G>A		intron_variant		1	NM_130810.4	P1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135125 AN: 151990 Hom.: 60916 Cov.: 30

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.889 AC: 135249 AN: 152108 Hom.: 60981 Cov.: 30 AF XY: 0.882 AC XY: 65538 AN XY: 74346

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.903

Gnomad4 OTH AF: 0.878

Alfa AF: 0.880 Hom.: 2848

Bravo AF: 0.884

Asia WGS AF: 0.665 AC: 2309 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	0.49
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4255730; hg19: chr15-55787781;