rs7181226

Positions:

• chr15-55437369-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_130810.4(DNAAF4):​c.893+2103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,096 control chromosomes in the GnomAD database, including 4,217 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 0.18 (4217 hom., cov: 33)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF4	NM_130810.4	c.893+2103A>G		intron_variant		ENST00000321149.7
DNAAF4-CCPG1	NR_037923.1	n.1148+2103A>G		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033559.3	c.893+2103A>G		intron_variant
DNAAF4	NM_001033560.2	c.893+2103A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF4	ENST00000321149.7	c.893+2103A>G		intron_variant		1	NM_130810.4	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27136 AN: 151978 Hom.: 4211 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.179 AC: 27177 AN: 152096 Hom.: 4217 Cov.: 33 AF XY: 0.176 AC XY: 13060 AN XY: 74370

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0857

Gnomad4 NFE AF: 0.0862

Gnomad4 OTH AF: 0.148

Alfa AF: 0.113 Hom.: 715

Bravo AF: 0.188

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: 48
DS_DG_spliceai		0.34		Position offset: -18

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

Publications

LitVar

Other links and lift over

dbSNP: rs7181226; hg19: chr15-55729567;