Variant 9-34458828-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_012144.4(DNAI1):c.-178G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 678,742 control chromosomes in the GnomAD database, including 515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 93 hom., cov: 32)

Exomes 𝑓: 0.018 ( 422 hom. )

Consequence

DNAI1
NM_012144.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

DNAI1 (HGNC:2954): (dynein axonemal intermediate chain 1) This gene encodes a member of the dynein intermediate chain family. The encoded protein is part of the dynein complex in respiratory cilia. The inner- and outer-arm dyneins, which bridge between the doublet microtubules in axonemes, are the force-generating proteins responsible for the sliding movement in axonemes. The intermediate and light chains, thought to form the base of the dynein arm, help mediate attachment and may also participate in regulating dynein activity. Mutations in this gene result in abnormal ciliary ultrastructure and function associated with primary ciliary dyskinesia and Kartagener syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

DNAI1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 9-34458828-G-C is Benign according to our data. Variant chr9-34458828-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 366679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAI1	NM_012144.4 linkuse as main transcript	c.-178G>C		5_prime_UTR_variant	1/20	ENST00000242317.9
DNAI1	NM_001281428.2 linkuse as main transcript	c.-178G>C		5_prime_UTR_variant	1/20

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI1	ENST00000242317.9 linkuse as main transcript	c.-178G>C	5_prime_UTR_variant	1/20	1	NM_012144.4		Q9UI46-1
DNAI1	ENST00000614641.4 linkuse as main transcript	c.-178G>C	5_prime_UTR_variant	1/20	5		P1
DNAI1	ENST00000470982.5 linkuse as main transcript	n.47+1368G>C	intron_variant, non_coding_transcript_variant		5
DNAI1	ENST00000437363.5 linkuse as main transcript		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0207

AC:

3157

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.0182

AC:

9558

AN:

526404

Hom.:

422

Cov.:

AF XY:

0.0172

AC XY:

4834

AN XY:

281806

show subpopulations

Gnomad4 AFR exome

AF:

0.0355

Gnomad4 AMR exome

AF:

0.0911

Gnomad4 ASJ exome

AF:

0.000169

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0225

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0208

AC:

3175

AN:

152338

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

1625

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0361

Gnomad4 AMR

AF:

0.0424

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.0265

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.0760

AC:

263

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.75

Splicing

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