rs60681706

chr3-129492226-A-G

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: 0.134

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
IFT122	NM_052989.3	c.2046+32A>G		intron_variant		ENST00000348417.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT122	ENST00000348417.7	c.2046+32A>G		intron_variant		1	NM_052989.3

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

GnomAD3 exomes AF: 0.0246 AC: 6187 AN: 251466 Hom.: 356 AF XY: 0.0263 AC XY: 3573 AN XY: 135910

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 SAS exome AF: 0.106

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

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00761

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.0150

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.00191

Gnomad4 OTH exome AF: 0.0172

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

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0183

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0196 Hom.: 29

Bravo AF: 0.0448

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.1
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs60681706; hg19: chr3-129211069;