rs117184646

Variant names:

• chr16-84154825-C-G
• rs117184646
• NM_178452.6:c.574+27C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-84154825-C-G
• chr16-84154825-C-T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.148
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.574+27C>G		intron	N/A	NP_848547.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.574+27C>G		intron	N/A	ENSP00000367815.5	Q8NEP3-1
	DNAAF1	ENST00000567918.5	TSL:1	n.574+27C>G		intron	N/A	ENSP00000455154.1	H3BP51
	DNAAF1	ENST00000963697.1		c.574+27C>G		intron	N/A	ENSP00000633756.1

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

GnomAD2 exomes AF: 0.0381 AC: 9558 AN: 250748 AF XY: 0.0291

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 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

African (AFR) AF: 0.00225 AC: 73 AN: 32408

American (AMR) AF: 0.237 AC: 10569 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25792

East Asian (EAS) AF: 0.0319 AC: 1260 AN: 39450

South Asian (SAS) AF: 0.00196 AC: 167 AN: 85226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5658

European-Non Finnish (NFE) AF: 0.000132 AC: 141 AN: 1067124

Other (OTH) AF: 0.00862 AC: 507 AN: 58812

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

African (AFR) AF: 0.00388 AC: 161 AN: 41540

American (AMR) AF: 0.150 AC: 2294 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0321 AC: 166 AN: 5178

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68028

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.00914 Hom.: 19

Bravo AF: 0.0296

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.36
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs117184646; hg19: chr16-84188430; COSMIC: COSV57577071; COSMIC: COSV57577071;