rs8111947

Variant names:

• chr19-48298169-T-C
• rs8111947
• NM_001364171.2:c.1404+8A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-48298169-T-C
• chr19-48298169-T-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.1404+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,610,912 control chromosomes in the GnomAD database, including 104,786 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 0.37 (10563 hom., cov: 30)
  • Exomes 𝑓: 0.35 (94223 hom.)
• Consequence: ODAD1 NM_001364171.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001091
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.32
• Publications: 11 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=-0.95).
• BP6: Variant 19-48298169-T-C is Benign according to our data. Variant chr19-48298169-T-C is described in ClinVar as Benign. ClinVar VariationId is 262486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 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.1404+8A>G		splice_region intron	N/A	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.1293+8A>G		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.1404+8A>G		splice_region intron	N/A	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.1293+8A>G		splice_region intron	N/A	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.1464+8A>G		splice_region intron	N/A	ENSP00000529843.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55257 AN: 150932 Hom.: 10542 Cov.: 30

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.364

GnomAD2 exomes AF: 0.318 AC: 79524 AN: 249742 AF XY: 0.324

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.442

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.368

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.353 AC: 515679 AN: 1459860 Hom.: 94223 Cov.: 42 AF XY: 0.352 AC XY: 255473 AN XY: 726314

African (AFR) AF: 0.448 AC: 14990 AN: 33464

American (AMR) AF: 0.186 AC: 8331 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11560 AN: 26122

East Asian (EAS) AF: 0.115 AC: 4576 AN: 39690

South Asian (SAS) AF: 0.290 AC: 24997 AN: 86236

European-Finnish (FIN) AF: 0.330 AC: 17128 AN: 51926

Middle Eastern (MID) AF: 0.386 AC: 2227 AN: 5766

European-Non Finnish (NFE) AF: 0.369 AC: 410665 AN: 1111612

Other (OTH) AF: 0.351 AC: 21205 AN: 60364

GnomAD4 genome AF: 0.366 AC: 55313 AN: 151052 Hom.: 10563 Cov.: 30 AF XY: 0.360 AC XY: 26564 AN XY: 73724

African (AFR) AF: 0.443 AC: 18230 AN: 41120

American (AMR) AF: 0.261 AC: 3961 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1528 AN: 3468

East Asian (EAS) AF: 0.128 AC: 645 AN: 5024

South Asian (SAS) AF: 0.276 AC: 1324 AN: 4790

European-Finnish (FIN) AF: 0.337 AC: 3520 AN: 10454

Middle Eastern (MID) AF: 0.400 AC: 116 AN: 290

European-Non Finnish (NFE) AF: 0.369 AC: 25020 AN: 67756

Other (OTH) AF: 0.363 AC: 758 AN: 2090

Alfa AF: 0.373 Hom.: 4598

Bravo AF: 0.362

Asia WGS AF: 0.212 AC: 743 AN: 3478

EpiCase AF: 0.375

EpiControl AF: 0.369

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.49
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.0040
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: rs8111947; hg19: chr19-48801426; COSMIC: COSV59558635;