rs10814116

chr9-34500881-C-T

Variant summary

Our verdict is Benign. Variant got -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:3
• 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

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/exons	MANE	UniProt
DNAI1	NM_012144.4	c.1019+42C>T		intron_variant		ENST00000242317.9
DNAI1	NM_001281428.2	c.1031+42C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI1	ENST00000242317.9	c.1019+42C>T		intron_variant		1	NM_012144.4
DNAI1	ENST00000614641.4	c.1031+42C>T		intron_variant		5		P1

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

GnomAD3 exomes AF: 0.198 AC: 49513 AN: 250246 Hom.: 5816 AF XY: 0.207 AC XY: 28007 AN XY: 135338

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

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

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 10, 2019

- -

Kartagener syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

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

Other links and lift over

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