Genetic Variant IGSF22:p.Ile1131Val (chr11-18707103-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_173588.4(IGSF22):c.3391A>G(p.Ile1131Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,551,224 control chromosomes in the GnomAD database, including 105,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7854 hom., cov: 32)

Exomes 𝑓: 0.37 ( 97857 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0990

Publications

42 publications found

Variant links:

Genes affected

IGSF22 (HGNC:26750): (immunoglobulin superfamily member 22)

IGSF22 links:

IGSF22-AS1 (HGNC:55511): (IGSF22 antisense RNA 1)

IGSF22-AS1 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 (MetaRNN=1.16656E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF22	NM_173588.4 link	c.3391A>G	p.Ile1131Val	missense_variant	Exon 21 of 23	ENST00000513874.6	NP_775859.4	Q8N9C0-2
IGSF22	XM_047426830.1 link	c.1465A>G	p.Ile489Val	missense_variant	Exon 8 of 10		XP_047282786.1
IGSF22	NR_160413.1 link	n.3147A>G		non_coding_transcript_exon_variant	Exon 19 of 21
IGSF22-AS1	NR_186353.1 link	n.623T>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6 link	c.3391A>G	p.Ile1131Val	missense_variant	Exon 21 of 23	5	NM_173588.4	ENSP00000421191.1		Q8N9C0-2

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43134

AN:

151984

Hom.:

7851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.325

AC:

50029

AN:

153960

AF XY:

0.321

show subpopulations

Gnomad AFR exome

AF:

0.0580

Gnomad AMR exome

AF:

0.390

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.365

AC:

510842

AN:

1399122

Hom.:

97857

Cov.:

AF XY:

0.361

AC XY:

249363

AN XY:

690090

show subpopulations

African (AFR)

AF:

0.0559

AC:

1765

AN:

31598

American (AMR)

AF:

0.379

AC:

13539

AN:

35688

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

7405

AN:

25180

East Asian (EAS)

AF:

0.162

AC:

5802

AN:

35738

South Asian (SAS)

AF:

0.211

AC:

16742

AN:

79206

European-Finnish (FIN)

AF:

0.465

AC:

22907

AN:

49246

Middle Eastern (MID)

AF:

0.235

AC:

1338

AN:

5698

European-Non Finnish (NFE)

AF:

0.391

AC:

422309

AN:

1078782

Other (OTH)

AF:

0.328

AC:

19035

AN:

57986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

17645

35291

52936

70582

88227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13100

26200

39300

52400

65500

<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:

0.284

AC:

43140

AN:

152102

Hom.:

7854

Cov.:

AF XY:

0.290

AC XY:

21548

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0703

AC:

2919

AN:

41536

American (AMR)

AF:

0.365

AC:

5576

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

995

AN:

3470

East Asian (EAS)

AF:

0.154

AC:

797

AN:

5182

South Asian (SAS)

AF:

0.200

AC:

963

AN:

4822

European-Finnish (FIN)

AF:

0.471

AC:

4983

AN:

10570

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.382

AC:

25958

AN:

67940

Other (OTH)

AF:

0.259

AC:

546

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1448

2896

4345

5793

7241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.341

Hom.:

31567

Bravo

AF:

0.266

TwinsUK

AF:

0.387

AC:

1434

ALSPAC

AF:

0.382

AC:

1473

ESP6500AA

AF:

0.0751

AC:

104

ESP6500EA

AF:

0.398

AC:

1267

ExAC

AF:

0.238

AC:

5771

Asia WGS

AF:

0.194

AC:

674

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.6

(source)

DANN

Benign

0.71

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.16

MetaRNN

Benign

0.00012

MetaSVM

Benign

-0.94

PhyloP100

-0.099

PrimateAI

Benign

0.38

PROVEAN

Benign

0.74

REVEL

Benign

0.037

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.010

MPC

0.18

ClinPred

0.0021

GERP RS

2.5

gMVP

0.16

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over