Variant 1-18362169-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032880.5(IGSF21):c.479G>A(p.Arg160His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,613,196 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R160C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

IGSF21
NM_032880.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.39

Variant links:

Genes affected

IGSF21 (HGNC:28246): (immunoglobin superfamily member 21) This gene encodes a protein which has two immunoglobulin (Ig) domains and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways. [provided by RefSeq, Sep 2011]

IGSF21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06726432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF21	NM_032880.5 link	c.479G>A	p.Arg160His	missense_variant	5/10	ENST00000251296.4	NP_116269.3	Q96ID5
IGSF21	XM_017002604.3 link	c.461G>A	p.Arg154His	missense_variant	5/10		XP_016858093.1
IGSF21	XM_017002605.1 link	c.248G>A	p.Arg83His	missense_variant	4/9		XP_016858094.1
IGSF21	XM_011542319.4 link	c.425-14141G>A		intron_variant			XP_011540621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGSF21	ENST00000251296.4 link	c.479G>A	p.Arg160His	missense_variant	5/10	1	NM_032880.5	ENSP00000251296.1	Q96ID5
IGSF21	ENST00000412684.3 link	n.336G>A		non_coding_transcript_exon_variant	4/6	5
IGSF21	ENST00000497331.2 link	n.803G>A		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000308

AC:

AN:

249608

Hom.:

AF XY:

0.000297

AC XY:

AN XY:

134906

show subpopulations

Gnomad AFR exome

AF:

0.000437

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00229

Gnomad SAS exome

AF:

0.000531

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000161

AC:

235

AN:

1460892

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

726614

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00154

Gnomad4 SAS exome

AF:

0.000722

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000263

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000194

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2023

The c.479G>A (p.R160H) alteration is located in exon 5 (coding exon 5) of the IGSF21 gene. This alteration results from a G to A substitution at nucleotide position 479, causing the arginine (R) at amino acid position 160 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.040

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.85

REVEL

Uncertain

0.40

Sift

Benign

0.052

Sift4G

Uncertain

0.0090

Polyphen

0.98

Vest4

0.90

MVP

0.84

MPC

0.94

ClinPred

0.11

GERP RS

4.6

Varity_R

0.19

gMVP

0.66

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

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