rs11999046

Variant names:

• chr9-34515208-G-C
• rs11999046
• NM_012144.4:c.1818+469G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012144.4(DNAI1):​c.1818+469G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,162 control chromosomes in the GnomAD database, including 4,824 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (4824 hom., cov: 32)
• Consequence: DNAI1 NM_012144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.1818+469G>C		intron_variant	Intron 18 of 19	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.1830+469G>C		intron_variant	Intron 18 of 19		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.1818+469G>C		intron_variant	Intron 18 of 19	1	NM_012144.4	ENSP00000242317.4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37639 AN: 152044 Hom.: 4820 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37652 AN: 152162 Hom.: 4824 Cov.: 32 AF XY: 0.244 AC XY: 18141 AN XY: 74402

African (AFR) AF: 0.236 AC: 9808 AN: 41506

American (AMR) AF: 0.221 AC: 3371 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3468

East Asian (EAS) AF: 0.0287 AC: 149 AN: 5188

South Asian (SAS) AF: 0.255 AC: 1234 AN: 4832

European-Finnish (FIN) AF: 0.220 AC: 2329 AN: 10578

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18908 AN: 67990

Other (OTH) AF: 0.255 AC: 537 AN: 2110

Alfa AF: 0.276 Hom.: 769

Bravo AF: 0.244

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		0.036
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: rs11999046; hg19: chr9-34515206;