rs56379561

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052989.3(IFT122):c.740+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,610,426 control chromosomes in the GnomAD database, including 12,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1709 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10357 hom. )

Consequence

IFT122
NM_052989.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.274

Publications

5 publications found

Variant links:

Genes affected

IFT122 (HGNC:13556): (intraflagellar transport 122) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This cytoplasmic protein contains seven WD repeats and an AF-2 domain which function by recruiting coregulatory molecules and in transcriptional activation. Mutations in this gene cause cranioectodermal dysplasia-1. A related pseudogene is located on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

IFT122 Gene-Disease associations (from GenCC):

cranioectodermal dysplasia 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
cranioectodermal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFT122 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 3-129467081-G-A is Benign according to our data. Variant chr3-129467081-G-A is described in ClinVar as Benign. ClinVar VariationId is 262273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT122	NM_052989.3 link	c.740+15G>A		intron_variant	Intron 8 of 29	ENST00000348417.7	NP_443715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000348417.7 link	c.740+15G>A		intron_variant	Intron 8 of 29	1	NM_052989.3	ENSP00000324005.4

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20157

AN:

152144

Hom.:

1703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0817

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.0390

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0942

Gnomad OTH

AF:

0.143

GnomAD2 exomes

AF:

0.117

AC:

29110

AN:

249336

AF XY:

0.124

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.0708

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.0769

Gnomad FIN exome

AF:

0.0387

Gnomad NFE exome

AF:

0.0955

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.108

AC:

157776

AN:

1458164

Hom.:

10357

Cov.:

AF XY:

0.113

AC XY:

81840

AN XY:

725496

show subpopulations

African (AFR)

AF:

0.230

AC:

7691

AN:

33388

American (AMR)

AF:

0.0739

AC:

3301

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

4376

AN:

26116

East Asian (EAS)

AF:

0.0644

AC:

2555

AN:

39680

South Asian (SAS)

AF:

0.248

AC:

21391

AN:

86140

European-Finnish (FIN)

AF:

0.0409

AC:

2166

AN:

52910

Middle Eastern (MID)

AF:

0.164

AC:

827

AN:

5040

European-Non Finnish (NFE)

AF:

0.0974

AC:

108133

AN:

1109998

Other (OTH)

AF:

0.122

AC:

7336

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

6220

12441

18661

24882

31102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4210

8420

12630

16840

21050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.133

AC:

20183

AN:

152262

Hom.:

1709

Cov.:

AF XY:

0.132

AC XY:

9835

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.220

AC:

9145

AN:

41510

American (AMR)

AF:

0.106

AC:

1627

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

576

AN:

3468

East Asian (EAS)

AF:

0.0811

AC:

421

AN:

5188

South Asian (SAS)

AF:

0.240

AC:

1159

AN:

4824

European-Finnish (FIN)

AF:

0.0390

AC:

414

AN:

10620

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0942

AC:

6410

AN:

68028

Other (OTH)

AF:

0.144

AC:

305

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

857

1715

2572

3430

4287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.123

Hom.:

300

Bravo

AF:

0.139

Asia WGS

AF:

0.204

AC:

714

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 13, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cranioectodermal dysplasia 1

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cranioectodermal dysplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.2

(source)

DANN

Benign

0.61

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over