Genetic Variant NM_130810.4:c.406-719A>G (chr15-55467880-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_130810.4(DNAAF4):c.406-719A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,908 control chromosomes in the GnomAD database, including 2,035 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 0.14 ( 2035 hom., cov: 32)

Consequence

DNAAF4
NM_130810.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.767

Publications

5 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=-0.72).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
DNAAF4	NM_130810.4 link	c.406-719A>G	intron_variant	Intron 4 of 9	ENST00000321149.7	NP_570722.2
DNAAF4	NM_001033560.2 link	c.406-719A>G	intron_variant	Intron 4 of 8		NP_001028732.1
DNAAF4	NM_001033559.3 link	c.406-719A>G	intron_variant	Intron 4 of 8		NP_001028731.1
DNAAF4-CCPG1	NR_037923.1 link	n.661-719A>G	intron_variant	Intron 3 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF4	ENST00000321149.7 link	c.406-719A>G		intron_variant	Intron 4 of 9	1	NM_130810.4	ENSP00000323275.3

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20933

AN:

151786

Hom.:

2031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0873

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.0109

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0860

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0861

Gnomad OTH

AF:

0.117

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

GnomAD4 genome

AF:

0.138

AC:

20964

AN:

151908

Hom.:

2035

Cov.:

AF XY:

0.137

AC XY:

10197

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.279

AC:

11562

AN:

41462

American (AMR)

AF:

0.0872

AC:

1328

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

420

AN:

3462

East Asian (EAS)

AF:

0.0109

AC:

AN:

5132

South Asian (SAS)

AF:

0.116

AC:

552

AN:

4772

European-Finnish (FIN)

AF:

0.0860

AC:

909

AN:

10570

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0861

AC:

5851

AN:

67960

Other (OTH)

AF:

0.117

AC:

247

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

892

1783

2675

3566

4458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.0996

Hom.:

3727

Bravo

AF:

0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.2

(source)

DANN

Benign

0.86

PhyloP100

0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over