rs11999046

chr9-34515208-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
DNAI1	NM_012144.4	c.1818+469G>C		intron_variant		ENST00000242317.9
DNAI1	NM_001281428.2	c.1830+469G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI1	ENST00000242317.9	c.1818+469G>C		intron_variant		1	NM_012144.4

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.255

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

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: rs11999046; hg19: chr9-34515206;