rs117184646

Positions:

• chr16-84154825-C-G

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.574+27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00985 in 1,564,714 control chromosomes in the GnomAD database, including 1,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (260 hom., cov: 32)
  • Exomes 𝑓: 0.0090 (1471 hom.)
• Consequence: DNAAF1 NM_178452.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148

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 16-84154825-C-G is Benign according to our data. Variant chr16-84154825-C-G is described in ClinVar as [Benign]. Clinvar id is 262956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF1	NM_178452.6	c.574+27C>G		intron_variant		ENST00000378553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF1	ENST00000378553.10	c.574+27C>G		intron_variant		1	NM_178452.6	P1
DNAAF1	ENST00000567918.5	c.574+27C>G		intron_variant, NMD_transcript_variant		1
DNAAF1	ENST00000563093.5	c.574+27C>G		intron_variant, NMD_transcript_variant		2
DNAAF1	ENST00000570298.5	n.728+27C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2678 AN: 152124 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.00389

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.0381 AC: 9558 AN: 250748 Hom.: 1202 AF XY: 0.0291 AC XY: 3951 AN XY: 135654

Gnomad AFR exome AF: 0.00403

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0373

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000256

Gnomad OTH exome AF: 0.0268

GnomAD4 exome AF: 0.00900 AC: 12718 AN: 1412472 Hom.: 1471 Cov.: 25 AF XY: 0.00771 AC XY: 5443 AN XY: 706082

Gnomad4 AFR exome AF: 0.00225

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0319

Gnomad4 SAS exome AF: 0.00196

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00862

GnomAD4 genome AF: 0.0177 AC: 2701 AN: 152242 Hom.: 260 Cov.: 32 AF XY: 0.0208 AC XY: 1550 AN XY: 74426

Gnomad4 AFR AF: 0.00388

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0321

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00914 Hom.: 19

Bravo AF: 0.0296

Asia WGS AF: 0.0250 AC: 88 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

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs117184646; hg19: chr16-84188430; COSMIC: COSV57577071; COSMIC: COSV57577071;