rs138412741

Variant names:

• chr9-34512215-G-A
• rs138412741
• NM_012144.4:c.1401+17G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_012144.4(DNAI1):​c.1401+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00916 in 1,613,914 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0093 (76 hom.)
• Consequence: DNAI1 NM_012144.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.374
• 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: ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 9-34512215-G-A is Benign according to our data. Variant chr9-34512215-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00747 (1138/152326) while in subpopulation NFE AF = 0.0107 (730/68030). AF 95% confidence interval is 0.0101. There are 7 homozygotes in GnomAd4. There are 588 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR,AD gene

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.1401+17G>A		intron	N/A	NP_036276.1	A0A140VJI0
	DNAI1	NM_001281428.2		c.1413+17G>A		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.1401+17G>A		intron	N/A	ENSP00000242317.4	Q9UI46-1
	DNAI1	ENST00000878474.1		c.1494+17G>A		intron	N/A	ENSP00000548533.1
	DNAI1	ENST00000614641.4	TSL:5	c.1413+17G>A		intron	N/A	ENSP00000480538.1	A0A087WWV9

Frequencies

GnomAD3 genomes AF: 0.00748 AC: 1138 AN: 152208 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00822 AC: 2067 AN: 251490 AF XY: 0.00826

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00645

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0213

Gnomad NFE exome AF: 0.0117

Gnomad OTH exome AF: 0.00749

GnomAD4 exome AF: 0.00934 AC: 13644 AN: 1461588 Hom.: 76 Cov.: 32 AF XY: 0.00929 AC XY: 6752 AN XY: 727148

African (AFR) AF: 0.00161 AC: 54 AN: 33474

American (AMR) AF: 0.00183 AC: 82 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00739 AC: 193 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00347 AC: 299 AN: 86250

European-Finnish (FIN) AF: 0.0217 AC: 1161 AN: 53420

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.0103 AC: 11402 AN: 1111732

Other (OTH) AF: 0.00707 AC: 427 AN: 60388

GnomAD4 genome AF: 0.00747 AC: 1138 AN: 152326 Hom.: 7 Cov.: 32 AF XY: 0.00789 AC XY: 588 AN XY: 74484

African (AFR) AF: 0.00168 AC: 70 AN: 41564

American (AMR) AF: 0.00372 AC: 57 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4826

European-Finnish (FIN) AF: 0.0205 AC: 218 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 730 AN: 68030

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00896 Hom.: 2

Bravo AF: 0.00598

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Kartagener syndrome (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.1
DANN	Benign	0.80
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

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: rs138412741; hg19: chr9-34512213;