rs138412741

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI1	NM_012144.4	c.1401+17G>A		intron_variant	Intron 14 of 19	ENST00000242317.9	NP_036276.1
DNAI1	NM_001281428.2	c.1413+17G>A		intron_variant	Intron 14 of 19		NP_001268357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI1	ENST00000242317.9	c.1401+17G>A		intron_variant	Intron 14 of 19	1	NM_012144.4	ENSP00000242317.4
DNAI1	ENST00000614641.4	c.1413+17G>A		intron_variant	Intron 14 of 19	5		ENSP00000480538.1
DNAI1	ENST00000470169.5	n.336+17G>A		intron_variant	Intron 2 of 5	5		ENSP00000434296.1

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

GnomAD3 exomes AF: 0.00822 AC: 2067 AN: 251490 Hom.: 15 AF XY: 0.00826 AC XY: 1123 AN XY: 135920

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 SAS exome AF: 0.00297

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

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.00739

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00347

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.00707

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

Gnomad4 AFR AF: 0.00168

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0205

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00912 Hom.: 2

Bravo AF: 0.00598

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 24, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kartagener syndrome Benign:1

Oct 11, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely 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	-0.29
CADD	Benign	7.1
DANN	Benign	0.80

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: rs138412741; hg19: chr9-34512213;