rs56177753

Variant names:

• chr19-48304144-C-T
• rs56177753
• NM_001364171.2:c.666-4G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-48304144-C-T
• chr19-48304144-C-A
• chr19-48304144-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001364171.2(ODAD1):​c.666-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,596,794 control chromosomes in the GnomAD database, including 58,330 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4245 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54085 hom.)
• Consequence: ODAD1 NM_001364171.2 splice_region, intron
• Scores: Splicing: ADA: 0.00008480
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.27
• Publications: 7 publications found

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ODAD1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 20

  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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 19-48304144-C-T is Benign according to our data. Variant chr19-48304144-C-T is described in ClinVar as Benign. ClinVar VariationId is 262503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364171.2. 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
	ODAD1	NM_001364171.2	MANE Select	c.666-4G>A		splice_region intron	N/A	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.555-4G>A		splice_region intron	N/A	NP_653178.3	Q96M63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.666-4G>A		splice_region intron	N/A	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.555-4G>A		splice_region intron	N/A	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.666-4G>A		splice_region intron	N/A	ENSP00000529843.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34289 AN: 151882 Hom.: 4241 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.236 AC: 56894 AN: 241302 AF XY: 0.235

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.269 AC: 388508 AN: 1444796 Hom.: 54085 Cov.: 38 AF XY: 0.266 AC XY: 190656 AN XY: 717010

African (AFR) AF: 0.117 AC: 3887 AN: 33190

American (AMR) AF: 0.214 AC: 9494 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5601 AN: 25816

East Asian (EAS) AF: 0.138 AC: 5412 AN: 39154

South Asian (SAS) AF: 0.166 AC: 14229 AN: 85738

European-Finnish (FIN) AF: 0.285 AC: 13641 AN: 47946

Middle Eastern (MID) AF: 0.200 AC: 1124 AN: 5620

European-Non Finnish (NFE) AF: 0.290 AC: 319971 AN: 1103370

Other (OTH) AF: 0.254 AC: 15149 AN: 59672

GnomAD4 genome AF: 0.226 AC: 34303 AN: 151998 Hom.: 4245 Cov.: 32 AF XY: 0.223 AC XY: 16534 AN XY: 74290

African (AFR) AF: 0.126 AC: 5212 AN: 41506

American (AMR) AF: 0.240 AC: 3665 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3468

East Asian (EAS) AF: 0.141 AC: 729 AN: 5156

South Asian (SAS) AF: 0.166 AC: 797 AN: 4794

European-Finnish (FIN) AF: 0.276 AC: 2905 AN: 10538

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19469 AN: 67966

Other (OTH) AF: 0.236 AC: 497 AN: 2106

Alfa AF: 0.208 Hom.: 1121

Bravo AF: 0.219

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.4
DANN	Benign	0.82
PhyloP100		1.3
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000085
dbscSNV1_RF	Benign	0.0
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: rs56177753; hg19: chr19-48807401; COSMIC: COSV59558243; COSMIC: COSV59558243;