rs180838420

Variant names:

• chr9-34458826-G-A
• rs180838420
• NM_012144.4:c.-180G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-34458826-G-A
• chr9-34458826-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS1_Supporting

The NM_012144.4(DNAI1):​c.-180G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 671,388 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: DNAI1 NM_012144.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• Publications: 0 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]

FAM219A (HGNC:19920): (family with sequence similarity 219 member A) The protein encoded by this gene has homologs that have been identified in mouse, macaque, etc organisms. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00194 (295/152348) while in subpopulation AFR AF = 0.00661 (275/41592). AF 95% confidence interval is 0.00597. There are 1 homozygotes in GnomAd4. There are 131 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.-180G>A		5_prime_UTR	Exon 1 of 20	NP_036276.1	A0A140VJI0
	DNAI1	NM_001281428.2		c.-180G>A		5_prime_UTR	Exon 1 of 20	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.-180G>A		5_prime_UTR	Exon 1 of 20	ENSP00000242317.4	Q9UI46-1
	DNAI1	ENST00000878474.1		c.-180G>A		5_prime_UTR	Exon 1 of 21	ENSP00000548533.1
	DNAI1	ENST00000614641.4	TSL:5	c.-180G>A		5_prime_UTR	Exon 1 of 20	ENSP00000480538.1	A0A087WWV9

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 295 AN: 152230 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00663

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.000225 AC: 117 AN: 519040 Hom.: 0 Cov.: 5 AF XY: 0.000195 AC XY: 54 AN XY: 277124

African (AFR) AF: 0.00590 AC: 87 AN: 14750

American (AMR) AF: 0.000349 AC: 11 AN: 31504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17386

East Asian (EAS) AF: 0.00 AC: 0 AN: 31400

South Asian (SAS) AF: 0.0000523 AC: 3 AN: 57388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2842

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 297118

Other (OTH) AF: 0.000559 AC: 16 AN: 28630

GnomAD4 genome AF: 0.00194 AC: 295 AN: 152348 Hom.: 1 Cov.: 32 AF XY: 0.00176 AC XY: 131 AN XY: 74514

African (AFR) AF: 0.00661 AC: 275 AN: 41592

American (AMR) AF: 0.00118 AC: 18 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.00201

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Kartagener syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.95
PhyloP100		2.6
PromoterAI		-0.11	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs180838420; hg19: chr9-34458824;