rs112218090

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001177701.3(IFT27):c.415C>T(p.Arg139Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,598,246 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts 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. R139Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0083 ( 25 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 14 hom. )

Consequence

IFT27
NM_001177701.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.44

Publications

3 publications found

Variant links:

Genes affected

IFT27 (HGNC:18626): (intraflagellar transport 27) This gene encodes a GTP-binding protein that is a core component of the intraflagellar transport complex B. Characterization of the similar Chlamydomonas protein indicates a function in cell cycle control. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

IFT27 links:

CACNG2-DT (HGNC:55682): (CACNG2 divergent transcript)

CACNG2-DT 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=0.0053834617).

BP6

Variant 22-36762951-G-A is Benign according to our data. Variant chr22-36762951-G-A is described in ClinVar as [Benign]. Clinvar id is 377288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00829 (1263/152340) while in subpopulation AFR AF = 0.0278 (1157/41566). AF 95% confidence interval is 0.0265. There are 25 homozygotes in GnomAd4. There are 598 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT27	NM_001177701.3 link	c.415C>T	p.Arg139Trp	missense_variant	Exon 6 of 7	ENST00000433985.7	NP_001171172.1	Q9BW83-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT27	ENST00000433985.7 link	c.415C>T	p.Arg139Trp	missense_variant	Exon 6 of 7	1	NM_001177701.3	ENSP00000393541.2		Q9BW83-1

Frequencies

GnomAD3 genomes

AF:

0.00824

AC:

1254

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.00213

AC:

520

AN:

244614

AF XY:

0.00155

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.000898

AC:

1299

AN:

1445906

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

575

AN XY:

717444

show subpopulations

African (AFR)

AF:

0.0290

AC:

962

AN:

33166

American (AMR)

AF:

0.00165

AC:

AN:

43580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26042

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39024

South Asian (SAS)

AF:

0.0000360

AC:

AN:

83370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53202

Middle Eastern (MID)

AF:

0.00210

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.0000998

AC:

110

AN:

1102036

Other (OTH)

AF:

0.00233

AC:

139

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00829

AC:

1263

AN:

152340

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

598

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0278

AC:

1157

AN:

41566

American (AMR)

AF:

0.00536

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68030

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00951

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0281

AC:

124

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00278

AC:

337

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 30, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.61

.;D;D

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.77

T;T;D

MetaRNN

Benign

0.0054

T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.7

.;M;.

PhyloP100

3.4

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.010

D;D;.

Polyphen

0.97

D;D;.

Vest4

0.47

MVP

0.79

MPC

0.38

ClinPred

0.033

GERP RS

5.5

Varity_R

0.42

gMVP

0.47

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs112218090

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