Variant chr22-50530559-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001014440.4(ODF3B):c.683A>G(p.His228Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000944 in 1,588,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

ODF3B
NM_001014440.4 missense, splice_region

Scores

Splicing: ADA: 0.0002309

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.194

Variant links:

Genes affected

ODF3B (HGNC:):

ODF3B links:

CIMAP1B (HGNC:34388): (ciliary microtubule associated protein 1B) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CIMAP1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048627466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF3B	NM_001014440.4 linkuse as main transcript	c.683A>G	p.His228Arg	missense_variant, splice_region_variant	7/7	ENST00000329363.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIMAP1B	ENST00000329363.9 linkuse as main transcript	c.683A>G	p.His228Arg	missense_variant, splice_region_variant	7/7	5	NM_001014440.4	P4	A8MYP8-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000450

AC:

AN:

200032

Hom.:

AF XY:

0.0000550

AC XY:

AN XY:

109140

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000614

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000696

AC:

AN:

1436832

Hom.:

Cov.:

AF XY:

0.00000842

AC XY:

AN XY:

712756

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000233

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000253

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.683A>G (p.H228R) alteration is located in exon 7 (coding exon 6) of the ODF3B gene. This alteration results from a A to G substitution at nucleotide position 683, causing the histidine (H) at amino acid position 228 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0018

T;.;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.39

T;T;.

M_CAP

Benign

0.0088

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

N;.;N

MutationTaster

Benign

1.0

D;D;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

0.26

N;N;N

REVEL

Benign

0.039

Sift

Benign

0.89

T;T;T

Sift4G

Benign

0.65

T;T;T

Polyphen

0.17

B;.;B

Vest4

0.30

MutPred

0.71

Gain of MoRF binding (P = 0.0106);.;Gain of MoRF binding (P = 0.0106);

MVP

0.16

MPC

0.50

ClinPred

0.060

GERP RS

1.2

Varity_R

0.047

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.20

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over