rs3138373

Variant names:

• chr3-129430178-T-C
• rs3138373
• ENST00000687461.1:n.145+360T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-129430178-T-C
• chr3-129430178-T-G

Variant summary

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

The ENST00000687461.1(IFT122):​n.145+360T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,196 control chromosomes in the GnomAD database, including 1,673 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 0.13 (1673 hom., cov: 33)
• Consequence: IFT122 ENST00000687461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000687461.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT122	ENST00000687461.1		n.145+360T>C		intron	N/A
	IFT122	ENST00000693654.1		n.212+360T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20002 AN: 152078 Hom.: 1668 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.132 AC: 20031 AN: 152196 Hom.: 1673 Cov.: 33 AF XY: 0.131 AC XY: 9765 AN XY: 74426

African (AFR) AF: 0.217 AC: 8986 AN: 41490

American (AMR) AF: 0.106 AC: 1619 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 578 AN: 3472

East Asian (EAS) AF: 0.0806 AC: 418 AN: 5186

South Asian (SAS) AF: 0.240 AC: 1156 AN: 4816

European-Finnish (FIN) AF: 0.0397 AC: 421 AN: 10600

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0944 AC: 6422 AN: 68010

Other (OTH) AF: 0.144 AC: 305 AN: 2112

Alfa AF: 0.107 Hom.: 1328

Bravo AF: 0.138

Asia WGS AF: 0.204 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.68
PhyloP100		-0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3138373; hg19: chr3-129149021;