rs10814116

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
• Publications: 5 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=-0.78).
• BP6: Variant 9-34500881-C-T is Benign according to our data. Variant chr9-34500881-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012144.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI1	NM_012144.4	MANE Select	c.1019+42C>T		intron	N/A	NP_036276.1
	DNAI1	NM_001281428.2		c.1031+42C>T		intron	N/A	NP_001268357.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI1	ENST00000242317.9	TSL:1 MANE Select	c.1019+42C>T		intron	N/A	ENSP00000242317.4
	DNAI1	ENST00000614641.4	TSL:5	c.1031+42C>T		intron	N/A	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

African (AFR) AF: 0.0433 AC: 1321 AN: 30482

American (AMR) AF: 0.0905 AC: 4033 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 3913 AN: 25284

East Asian (EAS) AF: 0.368 AC: 14419 AN: 39132

South Asian (SAS) AF: 0.274 AC: 22876 AN: 83478

European-Finnish (FIN) AF: 0.174 AC: 9271 AN: 53166

Middle Eastern (MID) AF: 0.176 AC: 866 AN: 4922

European-Non Finnish (NFE) AF: 0.216 AC: 214221 AN: 991706

Other (OTH) 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

African (AFR) AF: 0.0497 AC: 2066 AN: 41534

American (AMR) AF: 0.126 AC: 1921 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1889 AN: 5166

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4822

European-Finnish (FIN) AF: 0.178 AC: 1885 AN: 10602

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14530 AN: 67998

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.192 Hom.: 1918

Bravo AF: 0.153

Asia WGS AF: 0.297 AC: 1029 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Kartagener syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.60
PhyloP100		0.048
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: rs10814116; hg19: chr9-34500879; COSMIC: COSV54279845; COSMIC: COSV54279845;