16-84174729-G-T

Position:

chr16-84174729-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 163084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-84174729-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF1	NM_178452.6 linkuse as main transcript	c.1698+7G>T		splice_region_variant, intron_variant		ENST00000378553.10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF1	ENST00000378553.10 linkuse as main transcript	c.1698+7G>T	splice_region_variant, intron_variant		1	NM_178452.6	P1	Q8NEP3-1
DNAAF1	ENST00000563093.5 linkuse as main transcript	c.*260G>T	3_prime_UTR_variant, NMD_transcript_variant	11/11	2			Q8NEP3-3
DNAAF1	ENST00000563818.5 linkuse as main transcript	n.1375+7G>T	splice_region_variant, intron_variant, non_coding_transcript_variant		2
DNAAF1	ENST00000570298.5 linkuse as main transcript	n.4151+1G>T	splice_donor_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42642

AN:

151964

Hom.:

6990

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.337

AC:

84709

AN:

251360

Hom.:

15353

AF XY:

0.334

AC XY:

45442

AN XY:

135854

show subpopulations

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 SAS exome

AF:

0.264

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.:

AF XY:

0.338

AC XY:

245825

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0928

Gnomad4 AMR exome

AF:

0.460

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.281

AC:

42661

AN:

152082

Hom.:

7003

Cov.:

AF XY:

0.285

AC XY:

21181

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.282

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.344

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.316

Hom.:

6354

Bravo

AF:

0.279

Asia WGS

AF:

0.274

AC:

951

AN:

3478

EpiCase

AF:

0.332

EpiControl

AF:

0.338

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	1698+7G>T in intron 10 of DNAAF1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 34.2% (2945/8600) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs3826151). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Primary ciliary dyskinesia 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.94

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over