dbSNP rs11128623: IQSEC1:c.*2653A>G (chr3-12898330-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134382.3(IQSEC1):c.*2653A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 152,320 control chromosomes in the GnomAD database, including 1,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.081 ( 1028 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IQSEC1
NM_001134382.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.295

Publications

5 publications found

Variant links:

Genes affected

IQSEC1 (HGNC:29112): (IQ motif and Sec7 domain ArfGEF 1) Predicted to enable protein kinase binding activity. Predicted to be involved in several processes, including positive regulation of focal adhesion disassembly; positive regulation of keratinocyte migration; and regulation of postsynaptic neurotransmitter receptor internalization. Located in nucleolus. Implicated in intellectual developmental disorder with short stature and behavioral abnormalities. [provided by Alliance of Genome Resources, Apr 2022]

IQSEC1 Gene-Disease associations (from GenCC):

intellectual developmental disorder with short stature and behavioral abnormalities
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IQSEC1 links:

ENSG00000297478 (HGNC:):

ENSG00000297478 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC1	NM_001134382.3 link	c.*2653A>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000613206.2	NP_001127854.1	Q6DN90-3B4DGC5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IQSEC1	ENST00000613206.2 link	c.*2653A>G	3_prime_UTR_variant	Exon 14 of 14	2	NM_001134382.3	ENSP00000480301.1	Q6DN90-3
IQSEC1	ENST00000273221.8 link	c.*1060A>G	3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000273221.4	Q6DN90-1
IQSEC1	ENST00000646269.1 link	c.*1060A>G	3_prime_UTR_variant	Exon 14 of 14			ENSP00000496366.1	A0A2R8Y7T6
ENSG00000297478	ENST00000748200.1 link	n.374+14325T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0809

AC:

12311

AN:

152202

Hom.:

1015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0440

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.0286

Gnomad SAS

AF:

0.0281

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0301

Gnomad OTH

AF:

0.0611

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0811

AC:

12352

AN:

152320

Hom.:

1028

Cov.:

AF XY:

0.0803

AC XY:

5983

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.214

AC:

8887

AN:

41546

American (AMR)

AF:

0.0438

AC:

671

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3472

East Asian (EAS)

AF:

0.0287

AC:

149

AN:

5192

South Asian (SAS)

AF:

0.0280

AC:

135

AN:

4830

European-Finnish (FIN)

AF:

0.0239

AC:

254

AN:

10626

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0301

AC:

2048

AN:

68026

Other (OTH)

AF:

0.0605

AC:

128

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

516

1032

1548

2064

2580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0448

Hom.:

498

Bravo

AF:

0.0888

Asia WGS

AF:

0.0410

AC:

143

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.80

(source)

DANN

Benign

0.72

PhyloP100

0.29

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over