rs1075938

Positions:

• chr15-55498493-G-A

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.-164C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 920,258 control chromosomes in the GnomAD database, including 2,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (1445 hom., cov: 30)
  • Exomes 𝑓: 0.024 (900 hom.)
• Consequence: DNAAF4 NM_130810.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0740

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-55498493-G-A is Benign according to our data. Variant chr15-55498493-G-A is described in ClinVar as [Benign]. Clinvar id is 1280260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF4	NM_130810.4	c.-164C>T		5_prime_UTR_variant	2/10	ENST00000321149.7	NP_570722.2
DNAAF4-CCPG1	NR_037923.1	n.92C>T		non_coding_transcript_exon_variant	1/16
DNAAF4	NM_001033559.3	c.-164C>T		5_prime_UTR_variant	2/9		NP_001028731.1
DNAAF4	NM_001033560.2	c.-164C>T		5_prime_UTR_variant	2/9		NP_001028732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7	c.-164C>T		5_prime_UTR_variant	2/10	1	NM_130810.4	ENSP00000323275	P1
DNAAF4	ENST00000348518.4	c.-164C>T		5_prime_UTR_variant	1/9	5		ENSP00000299561	P1

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 12940 AN: 149822 Hom.: 1440 Cov.: 30

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0144

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00697

Gnomad EAS AF: 0.00923

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0594

GnomAD4 exome AF: 0.0243 AC: 18739 AN: 770308 Hom.: 900 Cov.: 11 AF XY: 0.0233 AC XY: 8996 AN XY: 386238

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.0208

Gnomad4 ASJ exome AF: 0.00943

Gnomad4 EAS exome AF: 0.00606

Gnomad4 SAS exome AF: 0.0175

Gnomad4 FIN exome AF: 0.0321

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0351

GnomAD4 genome AF: 0.0865 AC: 12978 AN: 149950 Hom.: 1445 Cov.: 30 AF XY: 0.0849 AC XY: 6201 AN XY: 73050

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.00697

Gnomad4 EAS AF: 0.00925

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0545 Hom.: 260

Bravo AF: 0.0948

Asia WGS AF: 0.0420 AC: 145 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.81

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: rs1075938; hg19: chr15-55790691;