rs2301570

Variant names:

• chr3-129476820-C-T
• rs2301570
• NM_052989.3:c.1147+19C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-129476820-C-T
• chr3-129476820-C-A

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.1147+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 1,613,730 control chromosomes in the GnomAD database, including 5,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1300 hom., cov: 32)
  • Exomes 𝑓: 0.063 (3872 hom.)
• Consequence: IFT122 NM_052989.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0220
• Publications: 13 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• 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=-0.86).
• BP6: Variant 3-129476820-C-T is Benign according to our data. Variant chr3-129476820-C-T is described in ClinVar as Benign. ClinVar VariationId is 262267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 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.1147+19C>T		intron	N/A	NP_443715.1	Q9HBG6-1
	IFT122	NM_052985.4		c.1300+19C>T		intron	N/A	NP_443711.2	Q9HBG6-5
	IFT122	NM_001410808.1		c.1147+19C>T		intron	N/A	NP_001397737.1	A0A8I5KSG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT122	ENST00000348417.7	TSL:1 MANE Select	c.1147+19C>T		intron	N/A	ENSP00000324005.4	Q9HBG6-1
	IFT122	ENST00000296266.7	TSL:1	c.1300+19C>T		intron	N/A	ENSP00000296266.3	Q9HBG6-5
	IFT122	ENST00000507564.5	TSL:1	c.1123+19C>T		intron	N/A	ENSP00000425536.1	Q9HBG6-6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16091 AN: 151996 Hom.: 1295 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0934

GnomAD2 exomes AF: 0.0750 AC: 18795 AN: 250692 AF XY: 0.0736

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.0339

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.0271

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0714

GnomAD4 exome AF: 0.0630 AC: 92122 AN: 1461614 Hom.: 3872 Cov.: 33 AF XY: 0.0643 AC XY: 46778 AN XY: 727088

African (AFR) AF: 0.232 AC: 7759 AN: 33464

American (AMR) AF: 0.0361 AC: 1615 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2776 AN: 26134

East Asian (EAS) AF: 0.162 AC: 6439 AN: 39692

South Asian (SAS) AF: 0.0975 AC: 8404 AN: 86232

European-Finnish (FIN) AF: 0.0285 AC: 1522 AN: 53414

Middle Eastern (MID) AF: 0.113 AC: 637 AN: 5662

European-Non Finnish (NFE) AF: 0.0525 AC: 58418 AN: 1111910

Other (OTH) AF: 0.0754 AC: 4552 AN: 60382

GnomAD4 genome AF: 0.106 AC: 16124 AN: 152116 Hom.: 1300 Cov.: 32 AF XY: 0.105 AC XY: 7789 AN XY: 74352

African (AFR) AF: 0.222 AC: 9183 AN: 41432

American (AMR) AF: 0.0628 AC: 961 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3470

East Asian (EAS) AF: 0.146 AC: 755 AN: 5174

South Asian (SAS) AF: 0.100 AC: 485 AN: 4828

European-Finnish (FIN) AF: 0.0300 AC: 317 AN: 10582

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0549 AC: 3737 AN: 68020

Other (OTH) AF: 0.0929 AC: 196 AN: 2110

Alfa AF: 0.0681 Hom.: 926

Bravo AF: 0.113

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Cranioectodermal dysplasia 1 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.39
PhyloP100		-0.022
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: rs2301570; hg19: chr3-129195663; COSMIC: COSV56210070; COSMIC: COSV56210070;