15-55498112-G-T

Position:

• chr15-55498112-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130810.4(DNAAF4):​c.123+95C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,581,588 control chromosomes in the GnomAD database, including 50,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (11492 hom., cov: 32)
  • Exomes 𝑓: 0.22 (39353 hom.)
• Consequence: DNAAF4 NM_130810.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.802

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-55498112-G-T is Benign according to our data. Variant chr15-55498112-G-T is described in ClinVar as [Benign]. Clinvar id is 1250366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.123+95C>A		intron_variant		ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2	c.123+95C>A		intron_variant			NP_001028732.1
DNAAF4	NM_001033559.3	c.123+95C>A		intron_variant			NP_001028731.1
DNAAF4-CCPG1	NR_037923.1	n.378+95C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.123+95C>A		intron_variant		1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50042 AN: 151952 Hom.: 11452 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.222 AC: 316861 AN: 1429518 Hom.: 39353 AF XY: 0.223 AC XY: 158522 AN XY: 711054

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.330 AC: 50133 AN: 152070 Hom.: 11492 Cov.: 32 AF XY: 0.324 AC XY: 24043 AN XY: 74316

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.290

Alfa AF: 0.209 Hom.: 2066

Bravo AF: 0.343

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.45

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: rs3743204; hg19: chr15-55790310; COSMIC: COSV58249893;