rs2311394

Variant names:

• chr3-129440996-A-G
• rs2311394
• NM_052989.3:c.41+625A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052989.3(IFT122):​c.41+625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,166 control chromosomes in the GnomAD database, including 2,859 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2859 hom., cov: 32)
• Consequence: IFT122 NM_052989.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052989.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT122	NM_052989.3	MANE Select	c.41+625A>G		intron	N/A	NP_443715.1
	IFT122	NM_052985.4		c.41+625A>G		intron	N/A	NP_443711.2
	IFT122	NM_001410808.1		c.41+625A>G		intron	N/A	NP_001397737.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT122	ENST00000348417.7	TSL:1 MANE Select	c.41+625A>G		intron	N/A	ENSP00000324005.4
	IFT122	ENST00000296266.7	TSL:1	c.41+625A>G		intron	N/A	ENSP00000296266.3
	IFT122	ENST00000507564.5	TSL:1	c.41+625A>G		intron	N/A	ENSP00000425536.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24569 AN: 152048 Hom.: 2850 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24608 AN: 152166 Hom.: 2859 Cov.: 32 AF XY: 0.161 AC XY: 11968 AN XY: 74418

African (AFR) AF: 0.318 AC: 13200 AN: 41460

American (AMR) AF: 0.122 AC: 1873 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3472

East Asian (EAS) AF: 0.0814 AC: 421 AN: 5172

South Asian (SAS) AF: 0.241 AC: 1162 AN: 4826

European-Finnish (FIN) AF: 0.0391 AC: 415 AN: 10614

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0951 AC: 6466 AN: 68006

Other (OTH) AF: 0.168 AC: 355 AN: 2114

Alfa AF: 0.145 Hom.: 718

Bravo AF: 0.173

Asia WGS AF: 0.215 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.51
PhyloP100		0.34
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: rs2311394; hg19: chr3-129159839;