chr16-84174729-G-T

Variant names:

• chr16-84174729-G-T
• rs3826151
• NM_178452.6:c.1698+7G>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.1698+7G>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.335 in 1,613,740 control chromosomes in the GnomAD database, including 94,086 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7003 hom., cov: 33)
  • Exomes 𝑓: 0.34 (87083 hom.)
• Consequence: DNAAF1 NM_178452.6 splice_region, intron
• Scores: Splicing: ADA: 0.001239
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.90
• Publications: 20 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=-0.77).
• BP6: Variant 16-84174729-G-T is Benign according to our data. Variant chr16-84174729-G-T is described in ClinVar as Benign. ClinVar VariationId is 163084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.378 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.1698+7G>T		splice_region intron	N/A	NP_848547.4
	DNAAF1	NM_001318756.1		c.990+7G>T		splice_region intron	N/A	NP_001305685.1	Q8NEP3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.1698+7G>T		splice_region intron	N/A	ENSP00000367815.5	Q8NEP3-1
	DNAAF1	ENST00000963697.1		c.1704+1G>T		splice_donor intron	N/A	ENSP00000633756.1
	DNAAF1	ENST00000963694.1		c.1698+7G>T		splice_region intron	N/A	ENSP00000633753.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42642 AN: 151964 Hom.: 6990 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.337 AC: 84709 AN: 251360 AF XY: 0.334

Gnomad AFR exome AF: 0.0994

Gnomad AMR exome AF: 0.468

Gnomad ASJ exome AF: 0.274

Gnomad EAS exome AF: 0.366

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.341 AC: 498515 AN: 1461658 Hom.: 87083 Cov.: 40 AF XY: 0.338 AC XY: 245825 AN XY: 727132

African (AFR) AF: 0.0928 AC: 3106 AN: 33478

American (AMR) AF: 0.460 AC: 20559 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 7221 AN: 26134

East Asian (EAS) AF: 0.365 AC: 14492 AN: 39690

South Asian (SAS) AF: 0.264 AC: 22741 AN: 86254

European-Finnish (FIN) AF: 0.358 AC: 19093 AN: 53394

Middle Eastern (MID) AF: 0.259 AC: 1496 AN: 5768

European-Non Finnish (NFE) AF: 0.351 AC: 390609 AN: 1111836

Other (OTH) AF: 0.318 AC: 19198 AN: 60388

GnomAD4 genome AF: 0.281 AC: 42661 AN: 152082 Hom.: 7003 Cov.: 33 AF XY: 0.285 AC XY: 21181 AN XY: 74338

African (AFR) AF: 0.104 AC: 4333 AN: 41506

American (AMR) AF: 0.386 AC: 5895 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1874 AN: 5174

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4814

European-Finnish (FIN) AF: 0.363 AC: 3830 AN: 10562

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23403 AN: 67962

Other (OTH) AF: 0.281 AC: 593 AN: 2110

Alfa AF: 0.303 Hom.: 11596

Bravo AF: 0.279

Asia WGS AF: 0.274 AC: 951 AN: 3478

EpiCase AF: 0.332

EpiControl AF: 0.338

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.040
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: rs3826151; hg19: chr16-84208335; COSMIC: COSV57576726; COSMIC: COSV57576726;