dbSNP rs4782899: DNAAF1:c.1699-41T>C (chr16-84175892-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178452.6(DNAAF1):c.1699-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,608,462 control chromosomes in the GnomAD database, including 99,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7320 hom., cov: 33)

Exomes 𝑓: 0.35 ( 92368 hom. )

Consequence

DNAAF1
NM_178452.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.566

Publications

14 publications found

Variant links:

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 13
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-84175892-T-C is Benign according to our data. Variant chr16-84175892-T-C is described in ClinVar as Benign. ClinVar VariationId is 262944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178452.6. 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
	DNAAF1	NM_178452.6	MANE Select	c.1699-41T>C		intron	N/A	NP_848547.4
	DNAAF1	NM_001318756.1		c.991-41T>C		intron	N/A	NP_001305685.1	Q8NEP3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.1699-41T>C	intron	N/A	ENSP00000367815.5	Q8NEP3-1
DNAAF1	ENST00000963697.1		c.1705-41T>C	intron	N/A	ENSP00000633756.1
DNAAF1	ENST00000963694.1		c.1699-41T>C	intron	N/A	ENSP00000633753.1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43732

AN:

152016

Hom.:

7306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.345

AC:

85630

AN:

248470

AF XY:

0.343

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.376

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.352

AC:

512111

AN:

1456330

Hom.:

92368

Cov.:

AF XY:

0.349

AC XY:

252637

AN XY:

724750

show subpopulations

African (AFR)

AF:

0.0967

AC:

3233

AN:

33450

American (AMR)

AF:

0.463

AC:

20723

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

7754

AN:

26112

East Asian (EAS)

AF:

0.378

AC:

14981

AN:

39680

South Asian (SAS)

AF:

0.269

AC:

23153

AN:

86122

European-Finnish (FIN)

AF:

0.360

AC:

18144

AN:

50424

Middle Eastern (MID)

AF:

0.273

AC:

1572

AN:

5762

European-Non Finnish (NFE)

AF:

0.363

AC:

402677

AN:

1109766

Other (OTH)

AF:

0.330

AC:

19874

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16550

33101

49651

66202

82752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12808

25616

38424

51232

64040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.288

AC:

43754

AN:

152132

Hom.:

7320

Cov.:

AF XY:

0.292

AC XY:

21674

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.108

AC:

4492

AN:

41522

American (AMR)

AF:

0.390

AC:

5950

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1050

AN:

3470

East Asian (EAS)

AF:

0.372

AC:

1920

AN:

5160

South Asian (SAS)

AF:

0.272

AC:

1312

AN:

4822

European-Finnish (FIN)

AF:

0.366

AC:

3873

AN:

10590

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24059

AN:

67980

Other (OTH)

AF:

0.292

AC:

617

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1546

3093

4639

6186

7732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.303

Hom.:

1399

Bravo

AF:

0.287

Asia WGS

AF:

0.283

AC:

984

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.1

(source)

DANN

Benign

0.62

PhyloP100

-0.57

PromoterAI

0.17

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over