16-84175892-T-C

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.566

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=-0.82).
• BP6: Variant 16-84175892-T-C is Benign according to our data. Variant chr16-84175892-T-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF1	NM_178452.6	c.1699-41T>C		intron_variant		ENST00000378553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF1	ENST00000378553.10	c.1699-41T>C		intron_variant		1	NM_178452.6	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43732 AN: 152016 Hom.: 7306 Cov.: 33

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

GnomAD3 exomes AF: 0.345 AC: 85630 AN: 248470 Hom.: 15825 AF XY: 0.343 AC XY: 46126 AN XY: 134674

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 SAS exome AF: 0.270

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.: 32 AF XY: 0.349 AC XY: 252637 AN XY: 724750

Gnomad4 AFR exome AF: 0.0967

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.288 AC: 43754 AN: 152132 Hom.: 7320 Cov.: 33 AF XY: 0.292 AC XY: 21674 AN XY: 74350

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.292

Alfa AF: 0.303 Hom.: 1399

Bravo AF: 0.287

Asia WGS AF: 0.283 AC: 984 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.1
Dann	Benign	0.62

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: rs4782899; hg19: chr16-84209498; COSMIC: COSV58988077; COSMIC: COSV58988077;