rs61736920

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

postaxial polydactyly type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
polydactyly, postaxial, type a7
Inheritance: AR Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

IQCE links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCE	NM_152558.5 link	c.212G>A	p.Arg71Gln	missense_variant	Exon 4 of 22	ENST00000402050.7	NP_689771.3	Q6IPM2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCE	ENST00000402050.7 link	c.212G>A	p.Arg71Gln	missense_variant	Exon 4 of 22	1	NM_152558.5	ENSP00000385597.2		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

GnomAD2 exomes

AF:

0.0180

AC:

4292

AN:

238124

AF XY:

0.0202

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 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

African (AFR)

AF:

0.00170

AC:

AN:

33470

American (AMR)

AF:

0.00318

AC:

142

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00608

AC:

159

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.0422

AC:

3641

AN:

86248

European-Finnish (FIN)

AF:

0.0866

AC:

3563

AN:

41166

Middle Eastern (MID)

AF:

0.0186

AC:

107

AN:

5766

European-Non Finnish (NFE)

AF:

0.0111

AC:

12291

AN:

1111906

Other (OTH)

AF:

0.0159

AC:

957

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1056

2113

3169

4226

5282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0157

AC:

2397

AN:

152232

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1447

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00181

AC:

AN:

41546

American (AMR)

AF:

0.00634

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.0409

AC:

197

AN:

4812

European-Finnish (FIN)

AF:

0.0965

AC:

1022

AN:

10586

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

957

AN:

68038

Other (OTH)

AF:

0.0133

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

124

248

371

495

619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0124

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

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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

(source)

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;.;.;.;.;.;.;.;.

PhyloP100

1.8

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs61736920

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