rs9657620

Positions:

• chr9-34512554-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000242317.9(DNAI1):​c.1489+130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 896,828 control chromosomes in the GnomAD database, including 73,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15819 hom., cov: 32)
  • Exomes 𝑓: 0.39 (57841 hom.)
• Consequence: DNAI1 ENST00000242317.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.326

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=-0.8).
• BP6: Variant 9-34512554-G-A is Benign according to our data. Variant chr9-34512554-G-A is described in ClinVar as [Benign]. Clinvar id is 1177022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.1489+130G>A		intron_variant		ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.1501+130G>A		intron_variant			NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.1489+130G>A		intron_variant		1	NM_012144.4	ENSP00000242317
DNAI1	ENST00000614641.4	c.1501+130G>A		intron_variant		5		ENSP00000480538	P1
DNAI1	ENST00000470169.5	c.426+130G>A		intron_variant, NMD_transcript_variant		5		ENSP00000434296

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67425 AN: 151862 Hom.: 15798 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.388 AC: 288916 AN: 744848 Hom.: 57841 AF XY: 0.390 AC XY: 151452 AN XY: 388360

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.444 AC: 67492 AN: 151980 Hom.: 15819 Cov.: 32 AF XY: 0.447 AC XY: 33226 AN XY: 74264

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.426

Alfa AF: 0.414 Hom.: 2199

Bravo AF: 0.446

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

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	-0.80
CADD	Benign	0.68
DANN	Benign	0.22

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: rs9657620; hg19: chr9-34512552;