rs79494390

Positions:

chr16-1520261-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014714.4(IFT140):c.3743T>C(p.Ile1248Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,614,174 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 59 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 56 hom. )

Consequence

IFT140
NM_014714.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 9.24

Variant links:

Genes affected

IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]

IFT140 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=0.008605152).

BP6

Variant 16-1520261-A-G is Benign according to our data. Variant chr16-1520261-A-G is described in ClinVar as [Benign]. Clinvar id is 317998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1520261-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT140	NM_014714.4 linkuse as main transcript	c.3743T>C	p.Ile1248Thr	missense_variant	28/31	ENST00000426508.7	NP_055529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT140	ENST00000426508.7 linkuse as main transcript	c.3743T>C	p.Ile1248Thr	missense_variant	28/31	5	NM_014714.4	ENSP00000406012	P1	Q96RY7-1
IFT140	ENST00000361339.9 linkuse as main transcript	c.1325T>C	p.Ile442Thr	missense_variant	10/13	1		ENSP00000354895		Q96RY7-2
IFT140	ENST00000565298.5 linkuse as main transcript	n.3567T>C		non_coding_transcript_exon_variant	16/19	2
IFT140	ENST00000397417.6 linkuse as main transcript	c.*2181T>C		3_prime_UTR_variant, NMD_transcript_variant	21/24	5		ENSP00000380562

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2423

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00837

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00483

AC:

1215

AN:

251490

Hom.:

AF XY:

0.00383

AC XY:

521

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0543

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000624

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00224

AC:

3272

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1523

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0553

Gnomad4 AMR exome

AF:

0.00420

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00283

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000402

Gnomad4 OTH exome

AF:

0.00532

GnomAD4 genome

AF:

0.0160

AC:

2442

AN:

152288

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1153

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0527

Gnomad4 AMR

AF:

0.00836

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00720

Hom.:

Bravo

AF:

0.0185

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0491

AC:

216

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00567

AC:

688

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Saldino-Mainzer syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.1

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.97

.;D

Vest4

0.84

MVP

0.74

MPC

0.32

ClinPred

0.033

GERP RS

6.0

Varity_R

0.39

gMVP

0.52

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