rs4796750

Variant names:

• chr17-41962526-A-G
• rs4796750
• NM_031421.5:c.1528+1060A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-41962526-A-G
• chr17-41962526-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031421.5(ODAD4):​c.1528+1060A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,998 control chromosomes in the GnomAD database, including 35,690 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (35690 hom., cov: 32)
• Consequence: ODAD4 NM_031421.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 15 publications found

Genes affected

ODAD4 (HGNC:25280): (outer dynein arm docking complex subunit 4) This gene encodes a tetratricopeptide repeat domain-containing protein that localizes to ciliary axonmenes and plays a role in the docking of the outer dynein arm to cilia. Mutations in this gene cause severely reduced ciliary motility and the disorder CILD35 (ciliary dyskinesia,primary, 35). Primary ciliary dyskinesia is often associated with recurrent respiratory infections, immotile spermatozoa, and situs inversus; an inversion in left-right body symmetry. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

ODAD4 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 35

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD4	NM_031421.5	c.1528+1060A>G		intron_variant	Intron 11 of 11	ENST00000377540.6	NP_113609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD4	ENST00000377540.6	c.1528+1060A>G		intron_variant	Intron 11 of 11	1	NM_031421.5	ENSP00000478589.1
ODAD4	ENST00000591658.5	n.*118+1060A>G		intron_variant	Intron 9 of 9	5		ENSP00000477931.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102006 AN: 151880 Hom.: 35680 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.714

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.671 AC: 102045 AN: 151998 Hom.: 35690 Cov.: 32 AF XY: 0.672 AC XY: 49962 AN XY: 74300

African (AFR) AF: 0.467 AC: 19316 AN: 41400

American (AMR) AF: 0.811 AC: 12393 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2881 AN: 3470

East Asian (EAS) AF: 0.844 AC: 4370 AN: 5178

South Asian (SAS) AF: 0.798 AC: 3845 AN: 4818

European-Finnish (FIN) AF: 0.614 AC: 6484 AN: 10564

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50315 AN: 67974

Other (OTH) AF: 0.710 AC: 1497 AN: 2108

Alfa AF: 0.722 Hom.: 112010

Bravo AF: 0.678

Asia WGS AF: 0.764 AC: 2660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.61
PhyloP100		0.26

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: rs4796750; hg19: chr17-40114544;