chr9-34485648-C-T

Variant names:

• chr9-34485648-C-T
• rs2274591
• NM_012144.4:c.261+131C>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.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
• 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: ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.81).
• BP6: Variant 9-34485648-C-T is Benign according to our data. Variant chr9-34485648-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI1	NM_012144.4	MANE Select	c.261+131C>T		intron	N/A	NP_036276.1	A0A140VJI0
	DNAI1	NM_001281428.2		c.261+131C>T		intron	N/A	NP_001268357.1	A0A087WWV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI1	ENST00000242317.9	TSL:1 MANE Select	c.261+131C>T		intron	N/A	ENSP00000242317.4	Q9UI46-1
	DNAI1	ENST00000878474.1		c.261+131C>T		intron	N/A	ENSP00000548533.1
	DNAI1	ENST00000614641.4	TSL:5	c.261+131C>T		intron	N/A	ENSP00000480538.1	A0A087WWV9

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

African (AFR) AF: 0.201 AC: 3646 AN: 18112

American (AMR) AF: 0.282 AC: 9398 AN: 33274

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 3576 AN: 20488

East Asian (EAS) AF: 0.322 AC: 10446 AN: 32400

South Asian (SAS) AF: 0.257 AC: 16512 AN: 64354

European-Finnish (FIN) AF: 0.158 AC: 7001 AN: 44276

Middle Eastern (MID) AF: 0.175 AC: 720 AN: 4114

European-Non Finnish (NFE) AF: 0.133 AC: 60711 AN: 457924

Other (OTH) AF: 0.175 AC: 6188 AN: 35328

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

African (AFR) AF: 0.198 AC: 8225 AN: 41438

American (AMR) AF: 0.240 AC: 3672 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1724 AN: 5172

South Asian (SAS) AF: 0.264 AC: 1275 AN: 4832

European-Finnish (FIN) AF: 0.176 AC: 1859 AN: 10544

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.136 AC: 9257 AN: 68004

Other (OTH) AF: 0.183 AC: 387 AN: 2110

Alfa AF: 0.154 Hom.: 304

Bravo AF: 0.183

Asia WGS AF: 0.283 AC: 982 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.6
DANN	Benign	0.51
PhyloP100		-0.097
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: rs2274591; hg19: chr9-34485646; COSMIC: COSV54278120;