rs60681706

Variant names:

• chr3-129492226-A-G
• rs60681706
• NM_052989.3:c.2046+32A>G

Variant summary

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

The NM_052989.3(IFT122):​c.2046+32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,563,420 control chromosomes in the GnomAD database, including 1,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (401 hom., cov: 32)
  • Exomes 𝑓: 0.012 (904 hom.)
• Consequence: IFT122 NM_052989.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.134
• Publications: 1 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-129492226-A-G is Benign according to our data. Variant chr3-129492226-A-G is described in ClinVar as Benign. ClinVar VariationId is 262269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT122	NM_052989.3	c.2046+32A>G		intron_variant	Intron 17 of 29	ENST00000348417.7	NP_443715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000348417.7	c.2046+32A>G		intron_variant	Intron 17 of 29	1	NM_052989.3	ENSP00000324005.4

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6386 AN: 152176 Hom.: 401 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.0339

GnomAD2 exomes AF: 0.0246 AC: 6187 AN: 251466 AF XY: 0.0263

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.00627

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.0156

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00221

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.0122 AC: 17167 AN: 1411126 Hom.: 904 Cov.: 24 AF XY: 0.0144 AC XY: 10156 AN XY: 705090

African (AFR) AF: 0.135 AC: 4315 AN: 31898

American (AMR) AF: 0.00761 AC: 340 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25844

East Asian (EAS) AF: 0.0150 AC: 589 AN: 39348

South Asian (SAS) AF: 0.103 AC: 8795 AN: 85128

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53390

Middle Eastern (MID) AF: 0.0105 AC: 60 AN: 5688

European-Non Finnish (NFE) AF: 0.00191 AC: 2040 AN: 1066514

Other (OTH) AF: 0.0172 AC: 1007 AN: 58664

GnomAD4 genome AF: 0.0420 AC: 6393 AN: 152294 Hom.: 401 Cov.: 32 AF XY: 0.0420 AC XY: 3131 AN XY: 74472

African (AFR) AF: 0.129 AC: 5341 AN: 41546

American (AMR) AF: 0.0144 AC: 220 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0183 AC: 95 AN: 5180

South Asian (SAS) AF: 0.107 AC: 516 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00215 AC: 146 AN: 68030

Other (OTH) AF: 0.0336 AC: 71 AN: 2116

Alfa AF: 0.0199 Hom.: 63

Bravo AF: 0.0448

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

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PreventionGenetics, part of Exact Sciences

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	-0.80
CADD	Benign	2.1
DANN	Benign	0.75
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60681706; hg19: chr3-129211069;