rs9657620

Variant names:

• chr9-34512554-G-A
• rs9657620
• NM_012144.4:c.1489+130G>A

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.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 NM_012144.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.326
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 CliVar as Benign. Clinvar id is 1177022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34512554-G-A is described in CliVar as Benign. Clinvar id is 1177022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34512554-G-A is described in CliVar as Benign. Clinvar id is 1177022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34512554-G-A is described in CliVar as Benign. Clinvar id is 1177022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34512554-G-A is described in CliVar as Benign. Clinvar id is 1177022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34512554-G-A is described in CliVar as Benign. Clinvar id is 1177022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34512554-G-A is described in CliVar 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 rank	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.1489+130G>A		intron_variant	Intron 15 of 19	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.1501+130G>A		intron_variant	Intron 15 of 19		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.1489+130G>A		intron_variant	Intron 15 of 19	1	NM_012144.4	ENSP00000242317.4
DNAI1	ENST00000614641.4	c.1501+130G>A		intron_variant	Intron 15 of 19	5		ENSP00000480538.1
DNAI1	ENST00000470169.5	n.424+130G>A		intron_variant	Intron 3 of 5	5		ENSP00000434296.1

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

African (AFR) AF: 0.590 AC: 11173 AN: 18942

American (AMR) AF: 0.498 AC: 17272 AN: 34652

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 8640 AN: 20882

East Asian (EAS) AF: 0.335 AC: 10926 AN: 32642

South Asian (SAS) AF: 0.465 AC: 30352 AN: 65308

European-Finnish (FIN) AF: 0.436 AC: 19501 AN: 44766

Middle Eastern (MID) AF: 0.394 AC: 1120 AN: 2844

European-Non Finnish (NFE) AF: 0.359 AC: 175367 AN: 488354

Other (OTH) AF: 0.400 AC: 14565 AN: 36458

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

African (AFR) AF: 0.585 AC: 24221 AN: 41438

American (AMR) AF: 0.463 AC: 7079 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1791 AN: 5154

South Asian (SAS) AF: 0.457 AC: 2200 AN: 4816

European-Finnish (FIN) AF: 0.452 AC: 4778 AN: 10560

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24510 AN: 67942

Other (OTH) AF: 0.426 AC: 899 AN: 2110

Alfa AF: 0.419 Hom.: 2334

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

Nov 11, 2018

GeneDx

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	-0.80
CADD	Benign	0.68
DANN	Benign	0.22
PhyloP100		-0.33
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

Other links and lift over

dbSNP: rs9657620; hg19: chr9-34512552;