Variant 7-2571607-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_152558.5(IQCE):c.212G>A(p.Arg71Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,601,648 control chromosomes in the GnomAD database, including 427 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 61 hom., cov: 33)

Exomes 𝑓: 0.014 ( 366 hom. )

Consequence

IQCE
NM_152558.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 1.85

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023100078).

BP6

Variant 7-2571607-G-A is Benign according to our data. Variant chr7-2571607-G-A is described in ClinVar as [Benign]. Clinvar id is 684526.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0157 (2397/152232) while in subpopulation SAS AF= 0.0409 (197/4812). AF 95% confidence interval is 0.0363. There are 61 homozygotes in gnomad4. There are 1447 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCE	NM_152558.5 linkuse as main transcript	c.212G>A	p.Arg71Gln	missense_variant	4/22	ENST00000402050.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCE	ENST00000402050.7 linkuse as main transcript	c.212G>A	p.Arg71Gln	missense_variant	4/22	1	NM_152558.5	A2	Q6IPM2-1

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2400

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0415

Gnomad FIN

AF:

0.0965

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0180

AC:

4292

AN:

238124

Hom.:

125

AF XY:

0.0202

AC XY:

2625

AN XY:

130260

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00302

Gnomad ASJ exome

AF:

0.00612

Gnomad EAS exome

AF:

0.000169

Gnomad SAS exome

AF:

0.0444

Gnomad FIN exome

AF:

0.0934

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0144

AC:

20918

AN:

1449416

Hom.:

366

Cov.:

AF XY:

0.0154

AC XY:

11082

AN XY:

721414

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.00608

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0422

Gnomad4 FIN exome

AF:

0.0866

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0157

AC:

2397

AN:

152232

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1447

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0409

Gnomad4 FIN

AF:

0.0965

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00711

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00311

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.0196

AC:

2367

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0128

EpiControl

AF:

0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Polydactyly, postaxial, type a7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpretted as Likely benign and reported on 10/30/2014 by GTR ID 320384. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

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

Eigen

Benign

-0.062

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.096

LIST_S2

Uncertain

0.89

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

MetaRNN

Benign

0.0023

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

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

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

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

REVEL

Benign

0.059

Sift

Benign

0.066

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

Sift4G

Uncertain

0.035

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

Polyphen

1.0

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

Vest4

0.15

MPC

0.34

ClinPred

0.017

GERP RS

3.4

Varity_R

0.054

gMVP

0.084

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