Genetic Variant DNAAF4:c.1047+7416A>T (chr15-55427489-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001033560.2(DNAAF4):c.1047+7416A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,036 control chromosomes in the GnomAD database, including 6,055 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 0.25 ( 6055 hom., cov: 31)

Consequence

DNAAF4
NM_001033560.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.896

Publications

6 publications found

Variant links:

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 links:

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

DNAAF4-CCPG1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033560.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF4	NM_001033560.2		c.1047+7416A>T		intron	N/A	NP_001028732.1	Q8WXU2-2
	DNAAF4-CCPG1	NR_037923.1		n.1408+5008A>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAAF4	ENST00000448430.6	TSL:1	c.1047+7416A>T	intron	N/A	ENSP00000403412.2	Q8WXU2-2
DNAAF4	ENST00000524160.5	TSL:2	n.*480+5008A>T	intron	N/A	ENSP00000428097.1	B4DY92
DNAAF4-CCPG1	ENST00000565113.5	TSL:2	n.1184+5008A>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38171

AN:

151918

Hom.:

6058

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0870

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.0691

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.268

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

GnomAD4 genome

AF:

0.251

AC:

38159

AN:

152036

Hom.:

6055

Cov.:

AF XY:

0.249

AC XY:

18514

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0868

AC:

3606

AN:

41536

American (AMR)

AF:

0.214

AC:

3270

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1005

AN:

3470

East Asian (EAS)

AF:

0.0693

AC:

359

AN:

5182

South Asian (SAS)

AF:

0.202

AC:

970

AN:

4808

European-Finnish (FIN)

AF:

0.352

AC:

3716

AN:

10542

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24206

AN:

67934

Other (OTH)

AF:

0.265

AC:

559

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1343

2685

4028

5370

6713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

516

Bravo

AF:

0.234

Asia WGS

AF:

0.129

AC:

450

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.46

PhyloP100

-0.90

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over