9-34485648-C-T

Variant names:

• chr9-34485648-C-T
• rs2274591
• NM_012144.4:c.261+131C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012144.4(DNAI1):​c.261+131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 862,312 control chromosomes in the GnomAD database, including 14,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2673 hom., cov: 32)
  • Exomes 𝑓: 0.17 (11503 hom.)
• Consequence: DNAI1 NM_012144.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0970

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-34485648-C-T is Benign according to our data. Variant chr9-34485648-C-T is described in ClinVar as [Benign]. Clinvar id is 1221067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.261+131C>T		intron_variant	Intron 4 of 19	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.261+131C>T		intron_variant	Intron 4 of 19		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.261+131C>T		intron_variant	Intron 4 of 19	1	NM_012144.4	ENSP00000242317.4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27286 AN: 151924 Hom.: 2675 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.166 AC: 118198 AN: 710270 Hom.: 11503 AF XY: 0.169 AC XY: 63067 AN XY: 372166

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.180 AC: 27308 AN: 152042 Hom.: 2673 Cov.: 32 AF XY: 0.185 AC XY: 13755 AN XY: 74314

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.183

Alfa AF: 0.154 Hom.: 304

Bravo AF: 0.183

Asia WGS AF: 0.283 AC: 982 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

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	-0.81
CADD	Benign	9.6
DANN	Benign	0.51

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: rs2274591; hg19: chr9-34485646; COSMIC: COSV54278120;