Variant X-131274799-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001555.5(IGSF1):c.3551G>A(p.Arg1184Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000908 in 1,209,760 control chromosomes in the GnomAD database, including 6 homozygotes. There are 330 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00079 ( 1 hom., 24 hem., cov: 23)

Exomes 𝑓: 0.00092 ( 5 hom. 306 hem. )

Consequence

IGSF1
NM_001555.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.668

Variant links:

Genes affected

IGSF1 (HGNC:5948): (immunoglobulin superfamily member 1) This gene encodes a member of the immunoglobulin-like domain-containing superfamily. Proteins in this superfamily contain varying numbers of immunoglobulin-like domains and are thought to participate in the regulation of interactions between cells. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

IGSF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076056123).

BP6

Variant X-131274799-C-T is Benign according to our data. Variant chrX-131274799-C-T is described in ClinVar as [Benign]. Clinvar id is 3039420.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000795 (89/111997) while in subpopulation EAS AF= 0.00957 (34/3551). AF 95% confidence interval is 0.00704. There are 1 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 24 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF1	NM_001555.5 linkuse as main transcript	c.3551G>A	p.Arg1184Gln	missense_variant	18/20	ENST00000361420.8	NP_001546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000361420.8 linkuse as main transcript	c.3551G>A	p.Arg1184Gln	missense_variant	18/20	1	NM_001555.5	ENSP00000355010	P4	Q8N6C5-1

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

AN:

111943

Hom.:

Cov.:

AF XY:

0.000704

AC XY:

AN XY:

34109

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000754

Gnomad EAS

AF:

0.00955

Gnomad SAS

AF:

0.000753

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000884

Gnomad OTH

AF:

0.00198

GnomAD3 exomes

AF:

0.00123

AC:

225

AN:

183484

Hom.:

AF XY:

0.00113

AC XY:

AN XY:

67918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000438

Gnomad ASJ exome

AF:

0.000534

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000647

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000920

AC:

1010

AN:

1097763

Hom.:

Cov.:

AF XY:

0.000843

AC XY:

306

AN XY:

363119

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000369

Gnomad4 ASJ exome

AF:

0.000464

Gnomad4 EAS exome

AF:

0.0176

Gnomad4 SAS exome

AF:

0.000369

Gnomad4 FIN exome

AF:

0.0000493

Gnomad4 NFE exome

AF:

0.000469

Gnomad4 OTH exome

AF:

0.000781

GnomAD4 genome

AF:

0.000795

AC:

AN:

111997

Hom.:

Cov.:

AF XY:

0.000702

AC XY:

AN XY:

34173

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000754

Gnomad4 EAS

AF:

0.00957

Gnomad4 SAS

AF:

0.000756

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000884

Gnomad4 OTH

AF:

0.00196

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000646

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.00121

AC:

147

EpiCase

AF:

0.000545

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IGSF1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 16, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

.;T;.;.

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.89

.;D;D;D

MetaRNN

Benign

0.0076

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.020

.;N;.;.

MutationTaster

Benign

0.95

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.060

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.14

T;T;T;T

Polyphen

1.0

D;D;.;D

Vest4

0.32

MVP

0.19

MPC

0.80

ClinPred

0.044

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over