rs2289965

Positions:

• chr11-18707103-T-C

Variant summary

Our verdict is Benign. Variant got -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. 13/17 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

Genes affected

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

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

TMEM86A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IGSF22	NM_173588.4	c.3391A>G	p.Ile1131Val	missense_variant	21/23	ENST00000513874.6	NP_775859.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF22	ENST00000513874.6	c.3391A>G	p.Ile1131Val	missense_variant	21/23	5	NM_173588.4	ENSP00000421191	P1
IGSF22	ENST00000504981.5	n.3731A>G		non_coding_transcript_exon_variant	20/20	1
IGSF22-AS1	ENST00000527285.1	n.567T>C		non_coding_transcript_exon_variant	1/3	3
IGSF22	ENST00000319338.6	c.*287A>G		3_prime_UTR_variant, NMD_transcript_variant	19/21	2		ENSP00000322422

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

GnomAD3 exomes AF: 0.325 AC: 50029 AN: 153960 Hom.: 9089 AF XY: 0.321 AC XY: 26192 AN XY: 81674

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 SAS exome AF: 0.208

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

Gnomad4 AFR exome AF: 0.0559

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.328

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

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.259

Alfa AF: 0.356 Hom.: 24133

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
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
MutationTaster	Benign	1.0	P
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

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

Other links and lift over

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