rs2289965

Variant names:

• chr11-18707103-T-C
• rs2289965
• NM_173588.4:c.3391A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 42 publications found

Genes affected

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

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

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	NM_173588.4	MANE Select	c.3391A>G	p.Ile1131Val	missense	Exon 21 of 23	NP_775859.4	Q8N9C0-2
	IGSF22	NR_160413.1		n.3147A>G		non_coding_transcript_exon	Exon 19 of 21
	IGSF22-AS1	NR_186353.1		n.623T>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF22	ENST00000513874.6	TSL:5 MANE Select	c.3391A>G	p.Ile1131Val	missense	Exon 21 of 23	ENSP00000421191.1	Q8N9C0-2
	IGSF22	ENST00000504981.5	TSL:1	n.3731A>G		non_coding_transcript_exon	Exon 20 of 20
	IGSF22	ENST00000319338.6	TSL:2	n.*287A>G		non_coding_transcript_exon	Exon 19 of 21	ENSP00000322422.6	Q8N9C0-1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43134 AN: 151984 Hom.: 7851 Cov.: 32

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

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.: 41 AF XY: 0.361 AC XY: 249363 AN XY: 690090

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

GnomAD4 genome AF: 0.284 AC: 43140 AN: 152102 Hom.: 7854 Cov.: 32 AF XY: 0.290 AC XY: 21548 AN XY: 74344

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: 72 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25958 AN: 67940

Other (OTH) AF: 0.259 AC: 546 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.6
DANN	Benign	0.71
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.00012	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.099
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.037
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.010
MPC		0.18
ClinPred		0.0021	T
GERP RS		2.5
gMVP		0.16
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289965; hg19: chr11-18728650; COSMIC: COSV55010740; COSMIC: COSV55010740;