chr9-34500881-C-T

Variant names:

• chr9-34500881-C-T
• rs10814116
• NM_012144.4:c.1019+42C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0480

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]

ACMG classification

Our verdict: Benign. The variant received -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
DNAI1	NM_012144.4	c.1019+42C>T		intron_variant	Intron 11 of 19	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.1031+42C>T		intron_variant	Intron 11 of 19		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.1019+42C>T		intron_variant	Intron 11 of 19	1	NM_012144.4	ENSP00000242317.4
DNAI1	ENST00000614641.4	c.1031+42C>T		intron_variant	Intron 11 of 19	5		ENSP00000480538.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24709 AN: 152084 Hom.: 2523 Cov.: 32

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

GnomAD2 exomes AF: 0.198 AC: 49513 AN: 250246 AF XY: 0.207

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 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

Gnomad4 AFR exome AF: 0.0433 AC: 1321 AN: 30482

Gnomad4 AMR exome AF: 0.0905 AC: 4033 AN: 44552

Gnomad4 ASJ exome AF: 0.155 AC: 3913 AN: 25284

Gnomad4 EAS exome AF: 0.368 AC: 14419 AN: 39132

Gnomad4 SAS exome AF: 0.274 AC: 22876 AN: 83478

Gnomad4 FIN exome AF: 0.174 AC: 9271 AN: 53166

Gnomad4 NFE exome AF: 0.216 AC: 214221 AN: 991706

Gnomad4 Remaining exome AF: 0.198 AC: 11103 AN: 55996

GnomAD4 genome AF: 0.162 AC: 24718 AN: 152202 Hom.: 2524 Cov.: 32 AF XY: 0.163 AC XY: 12097 AN XY: 74406

Gnomad4 AFR AF: 0.0497 AC: 0.0497424 AN: 0.0497424

Gnomad4 AMR AF: 0.126 AC: 0.125605 AN: 0.125605

Gnomad4 ASJ AF: 0.154 AC: 0.153691 AN: 0.153691

Gnomad4 EAS AF: 0.366 AC: 0.36566 AN: 0.36566

Gnomad4 SAS AF: 0.278 AC: 0.277893 AN: 0.277893

Gnomad4 FIN AF: 0.178 AC: 0.177797 AN: 0.177797

Gnomad4 NFE AF: 0.214 AC: 0.213683 AN: 0.213683

Gnomad4 OTH AF: 0.171 AC: 0.171402 AN: 0.171402

Alfa AF: 0.192 Hom.: 1918

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

Submissions by phenotype

not provided Benign:2

Apr 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
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

Publications

LitVar

Other links and lift over

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