chr9-34500881-C-T

Variant summary

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

The NM_012144.4(DNAI1):​c.1019+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,480,920 control chromosomes in the GnomAD database, including 34,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2524 hom., cov: 32)
Exomes 𝑓: 0.21 ( 31937 hom. )

Consequence

DNAI1
NM_012144.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0480
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]

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=-0.78).
BP6
Variant 9-34500881-C-T is Benign according to our data. Variant chr9-34500881-C-T is described in ClinVar as [Benign]. Clinvar id is 260194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAI1NM_012144.4 linkc.1019+42C>T intron_variant Intron 11 of 19 ENST00000242317.9 NP_036276.1 Q9UI46-1A0A140VJI0
DNAI1NM_001281428.2 linkc.1031+42C>T intron_variant Intron 11 of 19 NP_001268357.1 Q9UI46A0A087WWV9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAI1ENST00000242317.9 linkc.1019+42C>T intron_variant Intron 11 of 19 1 NM_012144.4 ENSP00000242317.4 Q9UI46-1
DNAI1ENST00000614641.4 linkc.1031+42C>T intron_variant Intron 11 of 19 5 ENSP00000480538.1 A0A087WWV9

Frequencies

GnomAD3 genomes
AF:
0.162
AC:
24709
AN:
152084
Hom.:
2523
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0497
Gnomad AMI
AF:
0.166
Gnomad AMR
AF:
0.126
Gnomad ASJ
AF:
0.154
Gnomad EAS
AF:
0.365
Gnomad SAS
AF:
0.278
Gnomad FIN
AF:
0.178
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.214
Gnomad OTH
AF:
0.167
GnomAD3 exomes
AF:
0.198
AC:
49513
AN:
250246
Hom.:
5816
AF XY:
0.207
AC XY:
28007
AN XY:
135338
show subpopulations
Gnomad AFR exome
AF:
0.0454
Gnomad AMR exome
AF:
0.0851
Gnomad ASJ exome
AF:
0.158
Gnomad EAS exome
AF:
0.374
Gnomad SAS exome
AF:
0.272
Gnomad FIN exome
AF:
0.175
Gnomad NFE exome
AF:
0.214
Gnomad OTH exome
AF:
0.190
GnomAD4 exome
AF:
0.212
AC:
282023
AN:
1328718
Hom.:
31937
Cov.:
21
AF XY:
0.215
AC XY:
143572
AN XY:
668244
show subpopulations
Gnomad4 AFR exome
AF:
0.0433
Gnomad4 AMR exome
AF:
0.0905
Gnomad4 ASJ exome
AF:
0.155
Gnomad4 EAS exome
AF:
0.368
Gnomad4 SAS exome
AF:
0.274
Gnomad4 FIN exome
AF:
0.174
Gnomad4 NFE exome
AF:
0.216
Gnomad4 OTH exome
AF:
0.198
GnomAD4 genome
AF:
0.162
AC:
24718
AN:
152202
Hom.:
2524
Cov.:
32
AF XY:
0.163
AC XY:
12097
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.0497
Gnomad4 AMR
AF:
0.126
Gnomad4 ASJ
AF:
0.154
Gnomad4 EAS
AF:
0.366
Gnomad4 SAS
AF:
0.278
Gnomad4 FIN
AF:
0.178
Gnomad4 NFE
AF:
0.214
Gnomad4 OTH
AF:
0.171
Alfa
AF:
0.196
Hom.:
1680
Bravo
AF:
0.153
Asia WGS
AF:
0.297
AC:
1029
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 10, 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

- -

Kartagener syndrome Benign:1
Jul 01, 2021
Genome-Nilou Lab
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
-0.78
CADD
Benign
6.2
DANN
Benign
0.60

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs10814116; hg19: chr9-34500879; COSMIC: COSV54279845; COSMIC: COSV54279845; API