Genetic Variant IQCE:p.Gly108Gly (chr7-2572256-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_152558.5(IQCE):c.324C>T(p.Gly108Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,100 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 68 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 50 hom. )

Consequence

IQCE
NM_152558.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.644

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 7-2572256-C-T is Benign according to our data. Variant chr7-2572256-C-T is described in ClinVar as [Benign]. Clinvar id is 783483.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.644 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCE	NM_152558.5 link	c.324C>T	p.Gly108Gly	synonymous_variant	Exon 5 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.324C>T	p.Gly108Gly	synonymous_variant	Exon 5 of 22	1	NM_152558.5	ENSP00000385597.2		Q6IPM2-1

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2328

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00385

AC:

960

AN:

249494

AF XY:

0.00291

show subpopulations

Gnomad AFR exome

AF:

0.0543

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00152

AC:

2222

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

966

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.0532

AC:

1781

AN:

33480

American (AMR)

AF:

0.00304

AC:

136

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000675

AC:

AN:

1111910

Other (OTH)

AF:

0.00344

AC:

208

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

110

221

331

442

552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0152

AC:

2323

AN:

152334

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1083

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0529

AC:

2199

AN:

41580

American (AMR)

AF:

0.00582

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68028

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

118

237

355

474

592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00722

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.6

(source)

DANN

Benign

0.58

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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7-2572256-C-T

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