rs9836202

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_052989.3(IFT122):c.3265+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,442,200 control chromosomes in the GnomAD database, including 76 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 43 hom. )

Consequence

IFT122
NM_052989.3 splice_region, intron

Scores

Splicing: ADA: 0.00007155

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.361

Publications

1 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=-0.67).

BP6

Variant 3-129515606-C-T is Benign according to our data. Variant chr3-129515606-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 343265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1955/152304) while in subpopulation AFR AF = 0.042 (1747/41552). AF 95% confidence interval is 0.0404. There are 33 homozygotes in GnomAd4. There are 922 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT122	NM_052989.3 link	c.3265+7C>T		splice_region_variant, intron_variant	Intron 26 of 29	ENST00000348417.7	NP_443715.1	Q9HBG6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000348417.7 link	c.3265+7C>T		splice_region_variant, intron_variant	Intron 26 of 29	1	NM_052989.3	ENSP00000324005.4		Q9HBG6-1

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1942

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0418

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00363

AC:

901

AN:

248392

AF XY:

0.00311

show subpopulations

Gnomad AFR exome

AF:

0.0445

Gnomad AMR exome

AF:

0.00320

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000481

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00164

AC:

2117

AN:

1289896

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

949

AN XY:

650074

show subpopulations

African (AFR)

AF:

0.0457

AC:

1314

AN:

28758

American (AMR)

AF:

0.00404

AC:

179

AN:

44330

Ashkenazi Jewish (ASJ)

AF:

0.00164

AC:

AN:

25024

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38610

South Asian (SAS)

AF:

0.000122

AC:

AN:

82142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53292

Middle Eastern (MID)

AF:

0.00458

AC:

AN:

5242

European-Non Finnish (NFE)

AF:

0.000305

AC:

292

AN:

957846

Other (OTH)

AF:

0.00468

AC:

256

AN:

54652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

108

216

323

431

539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0128

AC:

1955

AN:

152304

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

922

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0420

AC:

1747

AN:

41552

American (AMR)

AF:

0.00909

AC:

139

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000471

AC:

AN:

68010

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

184

277

369

461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00535

Hom.:

Bravo

AF:

0.0151

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cranioectodermal dysplasia 1

Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Mar 16, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Connective tissue disorder

Benign:1

Jul 01, 2019

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.5

(source)

DANN

Benign

0.88

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000072

dbscSNV1_RF

Benign

0.040

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

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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