Genetic Variant IGSF22:p.Ala94Pro (chr11-18721633-C-G) – 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.280G>C(p.Ala94Pro) variant causes a missense change. The variant allele was found at a frequency of 0.411 in 1,613,988 control chromosomes in the GnomAD database, including 139,576 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.36 ( 10567 hom., cov: 33)

Exomes 𝑓: 0.42 ( 129009 hom. )

Consequence

IGSF22
NM_173588.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.57

Publications

25 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=7.071793E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173588.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IGSF22	NM_173588.4	MANE Select	c.280G>C	p.Ala94Pro	missense	Exon 4 of 23	NP_775859.4
IGSF22	NR_160413.1		n.428G>C		non_coding_transcript_exon	Exon 4 of 21
IGSF22-AS1	NR_186353.1		n.785+14240C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IGSF22	ENST00000513874.6	TSL:5 MANE Select	c.280G>C	p.Ala94Pro	missense	Exon 4 of 23	ENSP00000421191.1
IGSF22	ENST00000504981.5	TSL:1	n.421G>C		non_coding_transcript_exon	Exon 4 of 20
IGSF22	ENST00000319338.6	TSL:2	n.280G>C		non_coding_transcript_exon	Exon 4 of 21	ENSP00000322422.6

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54605

AN:

152072

Hom.:

10561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.364

GnomAD2 exomes

AF:

0.421

AC:

104972

AN:

249462

AF XY:

0.421

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.584

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.416

AC:

608390

AN:

1461796

Hom.:

129009

Cov.:

AF XY:

0.417

AC XY:

303593

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.211

AC:

7075

AN:

33478

American (AMR)

AF:

0.572

AC:

25571

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

10147

AN:

26134

East Asian (EAS)

AF:

0.348

AC:

13817

AN:

39700

South Asian (SAS)

AF:

0.491

AC:

42328

AN:

86250

European-Finnish (FIN)

AF:

0.394

AC:

21039

AN:

53390

Middle Eastern (MID)

AF:

0.413

AC:

2380

AN:

5768

European-Non Finnish (NFE)

AF:

0.415

AC:

462010

AN:

1111966

Other (OTH)

AF:

0.398

AC:

24023

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

21583

43167

64750

86334

107917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14288

28576

42864

57152

71440

<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:

0.359

AC:

54652

AN:

152192

Hom.:

10567

Cov.:

AF XY:

0.360

AC XY:

26809

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.219

AC:

9099

AN:

41540

American (AMR)

AF:

0.443

AC:

6774

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1354

AN:

3472

East Asian (EAS)

AF:

0.327

AC:

1688

AN:

5156

South Asian (SAS)

AF:

0.492

AC:

2371

AN:

4820

European-Finnish (FIN)

AF:

0.386

AC:

4090

AN:

10600

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27975

AN:

67988

Other (OTH)

AF:

0.362

AC:

763

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1823

3646

5470

7293

9116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.360

Hom.:

3161

Bravo

AF:

0.360

TwinsUK

AF:

0.425

AC:

1575

ALSPAC

AF:

0.421

AC:

1621

ESP6500AA

AF:

0.217

AC:

865

ESP6500EA

AF:

0.394

AC:

3270

ExAC

AF:

0.410

AC:

49534

Asia WGS

AF:

0.376

AC:

1308

AN:

3476

EpiCase

AF:

0.403

EpiControl

AF:

0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.84

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.22

MetaRNN

Benign

0.00071

MetaSVM

Benign

-0.90

PhyloP100

5.6

PrimateAI

Benign

0.36

PROVEAN

Benign

2.9

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.054

MPC

0.29

ClinPred

0.025

GERP RS

4.4

gMVP

0.53

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over