15-55468377-T-C

Position:

• chr15-55468377-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.406-1216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,040 control chromosomes in the GnomAD database, including 25,921 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 0.57 (25921 hom., cov: 32)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.406-1216A>G		intron_variant		ENST00000321149.7	NP_570722.2
DNAAF4-CCPG1	NR_037923.1	n.661-1216A>G		intron_variant, non_coding_transcript_variant
DNAAF4	NM_001033559.3	c.406-1216A>G		intron_variant			NP_001028731.1
DNAAF4	NM_001033560.2	c.406-1216A>G		intron_variant			NP_001028732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.406-1216A>G		intron_variant		1	NM_130810.4	ENSP00000323275	P1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85994 AN: 151922 Hom.: 25903 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.566 AC: 86055 AN: 152040 Hom.: 25921 Cov.: 32 AF XY: 0.571 AC XY: 42478 AN XY: 74334

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.600

Alfa AF: 0.606 Hom.: 36063

Bravo AF: 0.565

Asia WGS AF: 0.783 AC: 2723 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.69

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: rs692691; hg19: chr15-55760575;