rs78056463

chr16-84150372-G-A

Variant summary

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

The NM_178452.6(DNAAF1):c.352+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,510,580 control chromosomes in the GnomAD database, including 728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (142 hom., cov: 33)
  • Exomes 𝑓: 0.025 (586 hom.)
• Consequence: DNAAF1 NM_178452.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.786

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-84150372-G-A is Benign according to our data. Variant chr16-84150372-G-A is described in ClinVar as [Benign]. Clinvar id is 262953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-84150372-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF1	NM_178452.6	c.352+30G>A		intron_variant		ENST00000378553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF1	ENST00000378553.10	c.352+30G>A		intron_variant		1	NM_178452.6	P1
DNAAF1	ENST00000567918.5	c.352+30G>A		intron_variant, NMD_transcript_variant		1
DNAAF1	ENST00000563093.5	c.352+30G>A		intron_variant, NMD_transcript_variant		2
DNAAF1	ENST00000570298.5	n.506+30G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5221 AN: 152176 Hom.: 143 Cov.: 33

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0320

GnomAD3 exomes AF: 0.0263 AC: 6587 AN: 249986 Hom.: 145 AF XY: 0.0274 AC XY: 3711 AN XY: 135216

Gnomad AFR exome AF: 0.0662

Gnomad AMR exome AF: 0.0176

Gnomad ASJ exome AF: 0.0309

Gnomad EAS exome AF: 0.000273

Gnomad SAS exome AF: 0.0492

Gnomad FIN exome AF: 0.00524

Gnomad NFE exome AF: 0.0245

Gnomad OTH exome AF: 0.0350

GnomAD4 exome AF: 0.0252 AC: 34161 AN: 1358286 Hom.: 586 Cov.: 21 AF XY: 0.0260 AC XY: 17701 AN XY: 681858

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0330

Gnomad4 EAS exome AF: 0.000153

Gnomad4 SAS exome AF: 0.0471

Gnomad4 FIN exome AF: 0.00589

Gnomad4 NFE exome AF: 0.0235

Gnomad4 OTH exome AF: 0.0299

GnomAD4 genome AF: 0.0343 AC: 5219 AN: 152294 Hom.: 142 Cov.: 33 AF XY: 0.0337 AC XY: 2513 AN XY: 74470

Gnomad4 AFR AF: 0.0672

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0384

Gnomad4 FIN AF: 0.00415

Gnomad4 NFE AF: 0.0232

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0322 Hom.: 29

Bravo AF: 0.0369

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.41
Dann	Benign	0.75

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: rs78056463; hg19: chr16-84183977;