Variant 11-118555043-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001168618.2(IFT46):c.301C>G(p.Pro101Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,613,680 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 61 hom. )

Consequence

IFT46
NM_001168618.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.35

Variant links:

Genes affected

IFT46 (HGNC:26146): (intraflagellar transport 46) Predicted to enable protein C-terminus binding activity. Predicted to be involved in cilium assembly; intraciliary transport; and protein stabilization. Predicted to act upstream of or within smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IFT46 links:

IFT46 (HGNC:):

IFT46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011911184).

BP6

Variant 11-118555043-G-C is Benign according to our data. Variant chr11-118555043-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642438.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT46	NM_001168618.2 linkuse as main transcript	c.301C>G	p.Pro101Ala	missense_variant	6/12	ENST00000264021.8	NP_001162089.1	Q9NQC8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT46	ENST00000264021.8 linkuse as main transcript	c.301C>G	p.Pro101Ala	missense_variant	6/12	1	NM_001168618.2	ENSP00000264021.3		Q9NQC8-1

Frequencies

GnomAD3 genomes

AF:

0.00660

AC:

1005

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00922

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00696

AC:

1749

AN:

251464

Hom.:

AF XY:

0.00703

AC XY:

955

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.0195

Gnomad NFE exome

AF:

0.00952

Gnomad OTH exome

AF:

0.00815

GnomAD4 exome

AF:

0.00828

AC:

12095

AN:

1461402

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

5988

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.00920

Gnomad4 OTH exome

AF:

0.00689

GnomAD4 genome

AF:

0.00661

AC:

1006

AN:

152278

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

539

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0230

Gnomad4 NFE

AF:

0.00922

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00824

Hom.:

Bravo

AF:

0.00486

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00687

AC:

ExAC

AF:

0.00717

AC:

870

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00931

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

IFT46: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;.;.;.;.;.;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D

MetaRNN

Benign

0.012

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.3

M;.;.;.;.;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-6.1

D;D;D;D;D;D;D

REVEL

Uncertain

0.54

Sift

Benign

0.033

D;D;D;D;D;D;T

Sift4G

Benign

0.13

T;T;T;.;.;D;.

Polyphen

1.0

D;D;D;.;.;.;.

Vest4

0.88

MVP

0.33

MPC

0.71

ClinPred

0.028

GERP RS

4.5

Varity_R

0.46

gMVP

0.49

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