rs61747073

Positions:

chr2-27459442-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000260570.8(IFT172):c.2723G>A(p.Arg908Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,614,152 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R908W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.012 ( 12 hom., cov: 32)

Exomes 𝑓: 0.018 ( 264 hom. )

Consequence

IFT172
ENST00000260570.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.190

Variant links:

Genes affected

IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

IFT172 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002185136).

BP6

Variant 2-27459442-C-T is Benign according to our data. Variant chr2-27459442-C-T is described in ClinVar as [Benign]. Clinvar id is 379641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-27459442-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0122 (1861/152278) while in subpopulation NFE AF= 0.0183 (1245/68030). AF 95% confidence interval is 0.0175. There are 12 homozygotes in gnomad4. There are 866 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT172	NM_015662.3 linkuse as main transcript	c.2723G>A	p.Arg908Gln	missense_variant	25/48	ENST00000260570.8	NP_056477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT172	ENST00000260570.8 linkuse as main transcript	c.2723G>A	p.Arg908Gln	missense_variant	25/48	1	NM_015662.3	ENSP00000260570	P1	Q9UG01-1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1861

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00323

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00581

Gnomad FIN

AF:

0.0266

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.0130

AC:

3264

AN:

251430

Hom.:

AF XY:

0.0134

AC XY:

1818

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00777

Gnomad FIN exome

AF:

0.0233

Gnomad NFE exome

AF:

0.0195

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0179

AC:

26104

AN:

1461874

Hom.:

264

Cov.:

AF XY:

0.0175

AC XY:

12749

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00245

Gnomad4 AMR exome

AF:

0.00494

Gnomad4 ASJ exome

AF:

0.00245

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00763

Gnomad4 FIN exome

AF:

0.0240

Gnomad4 NFE exome

AF:

0.0206

Gnomad4 OTH exome

AF:

0.0140

GnomAD4 genome

AF:

0.0122

AC:

1861

AN:

152278

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

866

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00322

Gnomad4 AMR

AF:

0.00589

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.0266

Gnomad4 NFE

AF:

0.0183

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.0158

AC:

136

ExAC

AF:

0.0133

AC:

1614

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0158

EpiControl

AF:

0.0167

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 08, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.069

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

0.90

REVEL

Benign

0.079

Sift

Benign

0.56

Sift4G

Benign

0.61

Polyphen

0.0020

Vest4

0.10

MPC

0.21

ClinPred

0.0073

GERP RS

0.40

Varity_R

0.015

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over