chr7-2571607-G-A

Variant names:

• chr7-2571607-G-A
• rs61736920
• NM_152558.5:c.212G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.85

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]

ACMG classification

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 rank	MANE	Protein	UniProt
IQCE	NM_152558.5	c.212G>A	p.Arg71Gln	missense_variant	Exon 4 of 22	ENST00000402050.7	NP_689771.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2400 AN: 152114 Hom.: 61 Cov.: 33

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

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.: 31 AF XY: 0.0154 AC XY: 11082 AN XY: 721414

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.: 61 Cov.: 33 AF XY: 0.0194 AC XY: 1447 AN XY: 74414

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.: 17

Bravo AF: 0.00711

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.00311 AC: 12

ESP6500EA AF: 0.0113 AC: 93

ExAC AF: 0.0196 AC: 2367

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.0128

EpiControl AF: 0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
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	N
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	T
MutationAssessor	Uncertain	2.4	.;M;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.35	T
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	T
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

Other links and lift over

dbSNP: rs61736920; hg19: chr7-2611241;