rs78056463

Variant names:

• chr16-84150372-G-A
• rs78056463
• NM_178452.6:c.352+30G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-84150372-G-A
• chr16-84150372-G-C

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.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:3
• Conservation: PhyloP100: -0.786
• Publications: 2 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• 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 16-84150372-G-A is Benign according to our data. Variant chr16-84150372-G-A is described in ClinVar as Benign. ClinVar VariationId is 262953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.352+30G>A		intron_variant	Intron 3 of 11	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10	c.352+30G>A		intron_variant	Intron 3 of 11	1	NM_178452.6	ENSP00000367815.5
DNAAF1	ENST00000567918.5	n.352+30G>A		intron_variant	Intron 3 of 6	1		ENSP00000455154.1
DNAAF1	ENST00000563093.5	n.352+30G>A		intron_variant	Intron 3 of 10	2		ENSP00000457373.1
DNAAF1	ENST00000570298.5	n.506+30G>A		intron_variant	Intron 3 of 10	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

GnomAD2 exomes AF: 0.0263 AC: 6587 AN: 249986 AF XY: 0.0274

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 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

African (AFR) AF: 0.0699 AC: 2186 AN: 31258

American (AMR) AF: 0.0181 AC: 809 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.0330 AC: 843 AN: 25518

East Asian (EAS) AF: 0.000153 AC: 6 AN: 39180

South Asian (SAS) AF: 0.0471 AC: 3971 AN: 84258

European-Finnish (FIN) AF: 0.00589 AC: 314 AN: 53288

Middle Eastern (MID) AF: 0.0677 AC: 379 AN: 5600

European-Non Finnish (NFE) AF: 0.0235 AC: 23952 AN: 1017614

Other (OTH) AF: 0.0299 AC: 1701 AN: 56982

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

African (AFR) AF: 0.0672 AC: 2793 AN: 41552

American (AMR) AF: 0.0262 AC: 401 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0384 AC: 185 AN: 4822

European-Finnish (FIN) AF: 0.00415 AC: 44 AN: 10610

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0232 AC: 1577 AN: 68036

Other (OTH) AF: 0.0312 AC: 66 AN: 2116

Alfa AF: 0.0268 Hom.: 93

Bravo AF: 0.0369

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.41
DANN	Benign	0.75
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78056463; hg19: chr16-84183977;