rs61742074

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015662.3(IFT172):c.4745T>C(p.Ile1582Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,614,106 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 3 hom., cov: 32)

Exomes 𝑓: 0.011 ( 131 hom. )

Consequence

IFT172
NM_015662.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0930

Publications

14 publications found

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:

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KRTCAP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050986707).

BP6

Variant 2-27446270-A-G is Benign according to our data. Variant chr2-27446270-A-G is described in ClinVar as Benign. ClinVar VariationId is 379765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00712 (1084/152314) while in subpopulation NFE AF = 0.0125 (849/68026). AF 95% confidence interval is 0.0118. There are 3 homozygotes in GnomAd4. There are 483 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT172	NM_015662.3 link	c.4745T>C	p.Ile1582Thr	missense_variant	Exon 43 of 48	ENST00000260570.8	NP_056477.1	Q9UG01-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT172	ENST00000260570.8 link	c.4745T>C	p.Ile1582Thr	missense_variant	Exon 43 of 48	1	NM_015662.3	ENSP00000260570.3		Q9UG01-1

Frequencies

GnomAD3 genomes

AF:

0.00712

AC:

1083

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00768

AC:

1931

AN:

251446

AF XY:

0.00804

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00286

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.0114

AC:

16714

AN:

1461792

Hom.:

131

Cov.:

AF XY:

0.0113

AC XY:

8222

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

33480

American (AMR)

AF:

0.00423

AC:

189

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000995

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00777

AC:

670

AN:

86258

European-Finnish (FIN)

AF:

0.00352

AC:

188

AN:

53420

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0136

AC:

15093

AN:

1111926

Other (OTH)

AF:

0.00793

AC:

479

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

746

1492

2239

2985

3731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

590

1180

1770

2360

2950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00712

AC:

1084

AN:

152314

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

483

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00250

AC:

104

AN:

41580

American (AMR)

AF:

0.00405

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.00767

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0125

AC:

849

AN:

68026

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00704

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0153

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0121

AC:

104

ExAC

AF:

0.00842

AC:

1022

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0102

EpiControl

AF:

0.00996

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 17, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 21, 2018

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IFT172: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.3

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.16

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.35

PhyloP100

0.093

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.5

REVEL

Benign

0.060

Sift

Benign

0.62

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.15

MVP

0.040

MPC

0.23

ClinPred

0.0028

GERP RS

-3.8

Varity_R

0.058

gMVP

0.16

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over