rs10470431

Variant names:

• chr3-129448400-A-G
• rs10470431
• NM_052989.3:c.42-1471A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-129448400-A-G
• chr3-129448400-A-T

Variant summary

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

The NM_052989.3(IFT122):​c.42-1471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,114 control chromosomes in the GnomAD database, including 13,556 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 0.34 (13556 hom., cov: 32)
• Consequence: IFT122 NM_052989.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT122	NM_052989.3	MANE Select	c.42-1471A>G		intron	N/A	NP_443715.1
	IFT122	NM_052985.4		c.42-1471A>G		intron	N/A	NP_443711.2
	IFT122	NM_001410808.1		c.42-1471A>G		intron	N/A	NP_001397737.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT122	ENST00000348417.7	TSL:1 MANE Select	c.42-1471A>G		intron	N/A	ENSP00000324005.4
	IFT122	ENST00000296266.7	TSL:1	c.42-1471A>G		intron	N/A	ENSP00000296266.3
	IFT122	ENST00000507564.5	TSL:1	c.42-1471A>G		intron	N/A	ENSP00000425536.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52054 AN: 151996 Hom.: 13512 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.343 AC: 52161 AN: 152114 Hom.: 13556 Cov.: 32 AF XY: 0.344 AC XY: 25611 AN XY: 74364

African (AFR) AF: 0.694 AC: 28792 AN: 41460

American (AMR) AF: 0.332 AC: 5076 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3322 AN: 5180

South Asian (SAS) AF: 0.379 AC: 1829 AN: 4824

European-Finnish (FIN) AF: 0.0734 AC: 778 AN: 10598

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10460 AN: 67984

Other (OTH) AF: 0.321 AC: 677 AN: 2110

Alfa AF: 0.267 Hom.: 1208

Bravo AF: 0.375

Asia WGS AF: 0.508 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.48
PhyloP100		-0.79
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: rs10470431; hg19: chr3-129167243;