rs2276611

Variant names:

• chr2-169584491-G-A
• rs2276611
• ENST00000462903.6:c.-76G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-169584491-G-A
• chr2-169584491-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 4P and 8B. PP3_Strong BA1

The ENST00000462903.6(PPIG):​c.-76G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.161 in 470,750 control chromosomes in the GnomAD database, including 6,741 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1870 hom., cov: 32)
  • Exomes 𝑓: 0.17 (4871 hom.)
• Consequence: PPIG ENST00000462903.6 5_prime_UTR
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• Publications: 21 publications found

Genes affected

PPIG (HGNC:14650): (peptidylprolyl isomerase G) Enables cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Involved in protein peptidyl-prolyl isomerization. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307322 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3	c.-70+1G>A		splice_donor_variant, intron_variant	Intron 1 of 13	ENST00000260970.8	NP_004783.2
PPIG	XM_005246967.2	c.-76G>A		5_prime_UTR_variant	Exon 1 of 14		XP_005247024.1
PPIG	XM_017005302.3	c.-70+1G>A		splice_donor_variant, intron_variant	Intron 1 of 11		XP_016860791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8	c.-70+1G>A		splice_donor_variant, intron_variant	Intron 1 of 13	1	NM_004792.3	ENSP00000260970.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23228 AN: 152064 Hom.: 1859 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.169 AC: 25547 AN: 151274 AF XY: 0.172

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.0821

Gnomad EAS exome AF: 0.199

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.165 AC: 52570 AN: 318566 Hom.: 4871 Cov.: 0 AF XY: 0.171 AC XY: 30723 AN XY: 180010

African (AFR) AF: 0.178 AC: 1528 AN: 8596

American (AMR) AF: 0.206 AC: 5584 AN: 27154

Ashkenazi Jewish (ASJ) AF: 0.0812 AC: 876 AN: 10782

East Asian (EAS) AF: 0.207 AC: 1905 AN: 9204

South Asian (SAS) AF: 0.245 AC: 14644 AN: 59722

European-Finnish (FIN) AF: 0.175 AC: 4743 AN: 27050

Middle Eastern (MID) AF: 0.104 AC: 289 AN: 2784

European-Non Finnish (NFE) AF: 0.132 AC: 20963 AN: 158956

Other (OTH) AF: 0.142 AC: 2038 AN: 14318

GnomAD4 genome AF: 0.153 AC: 23274 AN: 152184 Hom.: 1870 Cov.: 32 AF XY: 0.155 AC XY: 11557 AN XY: 74390

African (AFR) AF: 0.175 AC: 7273 AN: 41518

American (AMR) AF: 0.148 AC: 2266 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1095 AN: 5168

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4826

European-Finnish (FIN) AF: 0.176 AC: 1866 AN: 10576

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8802 AN: 68020

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.136 Hom.: 5104

Bravo AF: 0.151

TwinsUK AF: 0.122 AC: 451

ALSPAC AF: 0.136 AC: 526

ExAC AF: 0.158 AC: 3221

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Benign	0.27	N
PhyloP100		4.3
GERP RS		5.4
PromoterAI		-0.31	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=193/107	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.94
SpliceAI score (max)		0.98		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.90		Position offset: 6
DS_DL_spliceai		0.98		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2276611; hg19: chr2-170441001;