Variant chr7-2572233-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_152558.5(IQCE):c.301C>A(p.His101Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,614,126 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.016 ( 60 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 62 hom. )

Consequence

IQCE
NM_152558.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.780

Variant links:

Genes affected

IQCE (HGNC:29171): (IQ motif containing E) Involved in limb morphogenesis. Predicted to be extrinsic component of membrane. Predicted to be part of plasma membrane protein complex. [provided by Alliance of Genome Resources, Apr 2022]

IQCE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024162233).

BP6

Variant 7-2572233-C-A is Benign according to our data. Variant chr7-2572233-C-A is described in ClinVar as [Benign]. Clinvar id is 768134.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCE	NM_152558.5 linkuse as main transcript	c.301C>A	p.His101Asn	missense_variant	5/22	ENST00000402050.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCE	ENST00000402050.7 linkuse as main transcript	c.301C>A	p.His101Asn	missense_variant	5/22	1	NM_152558.5	A2	Q6IPM2-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2417

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00436

AC:

1089

AN:

249504

Hom.:

AF XY:

0.00329

AC XY:

446

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.00342

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000539

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00194

AC:

2835

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1252

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0568

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000335

Gnomad4 OTH exome

AF:

0.00482

GnomAD4 genome

AF:

0.0159

AC:

2429

AN:

152322

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1146

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0536

Gnomad4 AMR

AF:

0.00837

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.0188

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0445

AC:

179

ESP6500EA

AF:

0.000599

AC:

ExAC

AF:

0.00541

AC:

654

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.043

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

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.70

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

MetaRNN

Benign

0.0024

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

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

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

.;N;N;N;.;N;.;N;N;N

REVEL

Benign

0.029

Sift

Benign

0.29

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

Sift4G

Benign

0.12

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

Polyphen

0.59

P;P;.;P;.;.;.;P;.;.

Vest4

0.28

MVP

0.43

MPC

0.25

ClinPred

0.011

GERP RS

2.0

Varity_R

0.093

gMVP

0.097

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