7-2572244-T-C

Variant names:

• chr7-2572244-T-C
• rs2917751
• NM_152558.5:c.312T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_152558.5(IQCE):​c.312T>C​(p.Thr104Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,613,770 control chromosomes in the GnomAD database, including 452,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.71 (38908 hom., cov: 33)
  • Exomes 𝑓: 0.75 (413733 hom.)
• Consequence: IQCE NM_152558.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.220
• Publications: 20 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-2572244-T-C is Benign according to our data. Variant chr7-2572244-T-C is described in ClinVar as [Benign]. Clinvar id is 1300115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCE	NM_152558.5	c.312T>C	p.Thr104Thr	synonymous_variant	Exon 5 of 22	ENST00000402050.7	NP_689771.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCE	ENST00000402050.7	c.312T>C	p.Thr104Thr	synonymous_variant	Exon 5 of 22	1	NM_152558.5	ENSP00000385597.2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108125 AN: 152000 Hom.: 38877 Cov.: 33

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.692

GnomAD2 exomes AF: 0.729 AC: 181799 AN: 249464 AF XY: 0.732

Gnomad AFR exome AF: 0.635

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.700

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.820

Gnomad NFE exome AF: 0.757

Gnomad OTH exome AF: 0.734

GnomAD4 exome AF: 0.750 AC: 1096380 AN: 1461652 Hom.: 413733 Cov.: 46 AF XY: 0.751 AC XY: 546059 AN XY: 727130

African (AFR) AF: 0.627 AC: 20993 AN: 33474

American (AMR) AF: 0.718 AC: 32121 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 18476 AN: 26136

East Asian (EAS) AF: 0.503 AC: 19949 AN: 39694

South Asian (SAS) AF: 0.761 AC: 65601 AN: 86254

European-Finnish (FIN) AF: 0.819 AC: 43744 AN: 53412

Middle Eastern (MID) AF: 0.662 AC: 3820 AN: 5768

European-Non Finnish (NFE) AF: 0.762 AC: 847651 AN: 1111810

Other (OTH) AF: 0.729 AC: 44025 AN: 60384

GnomAD4 genome AF: 0.711 AC: 108217 AN: 152118 Hom.: 38908 Cov.: 33 AF XY: 0.714 AC XY: 53070 AN XY: 74368

African (AFR) AF: 0.634 AC: 26296 AN: 41496

American (AMR) AF: 0.712 AC: 10876 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2389 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2618 AN: 5164

South Asian (SAS) AF: 0.743 AC: 3577 AN: 4814

European-Finnish (FIN) AF: 0.825 AC: 8743 AN: 10592

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.757 AC: 51467 AN: 67988

Other (OTH) AF: 0.694 AC: 1468 AN: 2114

Alfa AF: 0.732 Hom.: 16294

Bravo AF: 0.697

Asia WGS AF: 0.645 AC: 2248 AN: 3478

EpiCase AF: 0.747

EpiControl AF: 0.741

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

IQCE-related disorder Benign:1

Feb 01, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Polydactyly, postaxial, type a7 Benign:1

Aug 19, 2021

Genome-Nilou Lab

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	-0.78
CADD	Benign	5.7
DANN	Benign	0.53
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2917751; hg19: chr7-2611878; COSMIC: COSV58078565;