chr2-27446270-A-G

Position:

chr2-27446270-A-G

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 made for transcript

Verdict is Benign. Variant got -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 id is 379765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-27446270-A-G is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT172	NM_015662.3 linkuse as main transcript	c.4745T>C	p.Ile1582Thr	missense_variant	43/48	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.4745T>C	p.Ile1582Thr	missense_variant	43/48	1	NM_015662.3	ENSP00000260570	P1	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

GnomAD3 exomes

AF:

0.00768

AC:

1931

AN:

251446

Hom.:

AF XY:

0.00804

AC XY:

1092

AN XY:

135890

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 SAS exome

AF:

0.00758

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

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00777

Gnomad4 FIN exome

AF:

0.00352

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.00793

GnomAD4 genome

AF:

0.00712

AC:

1084

AN:

152314

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

483

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.0109

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

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 17, 2017	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	IFT172: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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

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

MutationTaster

Benign

0.90

N;D

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

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