9-34460032-C-G

Variant names:

• chr9-34460032-C-G
• rs4879792
• NM_012144.4:c.48+979C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012144.4(DNAI1):​c.48+979C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,086 control chromosomes in the GnomAD database, including 28,962 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 0.61 (28962 hom., cov: 32)
• Consequence: DNAI1 NM_012144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.48+979C>G		intron_variant	Intron 1 of 19	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.48+979C>G		intron_variant	Intron 1 of 19		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.48+979C>G		intron_variant	Intron 1 of 19	1	NM_012144.4	ENSP00000242317.4
DNAI1	ENST00000614641.4	c.48+979C>G		intron_variant	Intron 1 of 19	5		ENSP00000480538.1
DNAI1	ENST00000437363.5	c.48+979C>G		intron_variant	Intron 1 of 8	5		ENSP00000395396.1
DNAI1	ENST00000470982.5	n.47+2572C>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92715 AN: 151968 Hom.: 28919 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.610 AC: 92811 AN: 152086 Hom.: 28962 Cov.: 32 AF XY: 0.614 AC XY: 45609 AN XY: 74332

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.579

Alfa AF: 0.587 Hom.: 3347

Bravo AF: 0.612

Asia WGS AF: 0.553 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.079
DANN	Benign	0.62

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: rs4879792; hg19: chr9-34460030;