7-2572233-C-A

Variant names:

• chr7-2572233-C-A
• rs11976972
• NM_152558.5:c.301C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152558.5(IQCE):​c.301C>A​(p.His101Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,614,126 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (60 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (62 hom.)
• Consequence: IQCE NM_152558.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.780
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024162233).
• BP6: Variant 7-2572233-C-A is Benign according to our data. Variant chr7-2572233-C-A is described in ClinVar as Benign. ClinVar VariationId is 768134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152558.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCE	NM_152558.5	MANE Select	c.301C>A	p.His101Asn	missense	Exon 5 of 22	NP_689771.3
	IQCE	NM_001287499.2		c.301C>A	p.His101Asn	missense	Exon 5 of 21	NP_001274428.1	A0A087WX45
	IQCE	NM_001287500.2		c.253C>A	p.His85Asn	missense	Exon 4 of 20	NP_001274429.1	A0A087WX19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCE	ENST00000402050.7	TSL:1 MANE Select	c.301C>A	p.His101Asn	missense	Exon 5 of 22	ENSP00000385597.2	Q6IPM2-1
	IQCE	ENST00000623361.3	TSL:1	c.106C>A	p.His36Asn	missense	Exon 3 of 20	ENSP00000485601.1	Q6IPM2-2
	IQCE	ENST00000325997.13	TSL:1	n.*78C>A		non_coding_transcript_exon	Exon 3 of 20	ENSP00000314011.10	X5D7Y5

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2417 AN: 152204 Hom.: 60 Cov.: 33

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00436 AC: 1089 AN: 249504 AF XY: 0.00329

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.00342

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000539

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00194 AC: 2835 AN: 1461804 Hom.: 62 Cov.: 30 AF XY: 0.00172 AC XY: 1252 AN XY: 727200

African (AFR) AF: 0.0568 AC: 1901 AN: 33470

American (AMR) AF: 0.00425 AC: 190 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86258

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53416

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.000335 AC: 372 AN: 1111946

Other (OTH) AF: 0.00482 AC: 291 AN: 60394

GnomAD4 genome AF: 0.0159 AC: 2429 AN: 152322 Hom.: 60 Cov.: 33 AF XY: 0.0154 AC XY: 1146 AN XY: 74486

African (AFR) AF: 0.0536 AC: 2229 AN: 41570

American (AMR) AF: 0.00837 AC: 128 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68038

Other (OTH) AF: 0.0161 AC: 34 AN: 2110

Alfa AF: 0.00594 Hom.: 48

Bravo AF: 0.0188

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0445 AC: 179

ESP6500EA AF: 0.000599 AC: 5

ExAC AF: 0.00541 AC: 654

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.78
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.029
Sift	Benign	0.29	T
Sift4G	Benign	0.12	T
Polyphen		0.59	P
Vest4		0.28
MVP		0.43
MPC		0.25
ClinPred		0.011	T
GERP RS		2.0
Varity_R		0.093
gMVP		0.097
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11976972; hg19: chr7-2611867;