dbSNP rs9211: IQSEC1:c.*2936C>T (chr3-12898047-G-A) – 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.*2936C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,264 control chromosomes in the GnomAD database, including 50,208 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 0.80 ( 50203 hom., cov: 34)

Exomes 𝑓: 0.72 ( 5 hom. )

Consequence

IQSEC1
NM_001134382.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.623

Publications

15 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 = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC1	NM_001134382.3 link	c.*2936C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000613206.2	NP_001127854.1	Q6DN90-3B4DGC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQSEC1	ENST00000613206.2 link	c.*2936C>T		3_prime_UTR_variant	Exon 14 of 14	2	NM_001134382.3	ENSP00000480301.1		Q6DN90-3

Frequencies

GnomAD3 genomes

AF:

0.805

AC:

122393

AN:

152130

Hom.:

50152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.919

Gnomad AMI

AF:

0.825

Gnomad AMR

AF:

0.706

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.788

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.805

Gnomad OTH

AF:

0.777

GnomAD4 exome

AF:

0.722

AC:

AN:

Hom.:

Cov.:

AF XY:

0.857

AC XY:

AN XY:

show subpopulations

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:

0.600

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.805

AC:

122494

AN:

152246

Hom.:

50203

Cov.:

AF XY:

0.797

AC XY:

59349

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.919

AC:

38173

AN:

41548

American (AMR)

AF:

0.706

AC:

10800

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.753

AC:

2616

AN:

3472

East Asian (EAS)

AF:

0.387

AC:

2001

AN:

5170

South Asian (SAS)

AF:

0.665

AC:

3212

AN:

4830

European-Finnish (FIN)

AF:

0.788

AC:

8357

AN:

10610

Middle Eastern (MID)

AF:

0.709

AC:

207

AN:

292

European-Non Finnish (NFE)

AF:

0.805

AC:

54734

AN:

68004

Other (OTH)

AF:

0.776

AC:

1643

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1161

2322

3482

4643

5804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.796

Hom.:

30398

Bravo

AF:

0.805

Asia WGS

AF:

0.574

AC:

2000

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

0.48

(source)

DANN

Benign

0.43

PhyloP100

-0.62

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over