rs3213646

Variant names:

• chr16-20798745-T-C
• rs3213646
• NM_001142725.2:c.1055A>G

Variant summary

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

The NM_001142725.2(ERI2):​c.1055A>G​(p.Tyr352Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,551,326 control chromosomes in the GnomAD database, including 233,006 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.43 (16403 hom., cov: 32)
  • Exomes 𝑓: 0.54 (216603 hom.)
• Consequence: ERI2 NM_001142725.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 29 publications found

Genes affected

ERI2 (HGNC:30541): (ERI1 exoribonuclease family member 2) Predicted to enable 3'-5'-exoribonuclease activity. Predicted to be involved in exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2722978E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERI2	NM_001142725.2	c.1055A>G	p.Tyr352Cys	missense_variant	Exon 9 of 9	ENST00000357967.9	NP_001136197.1
ERI2	NM_080663.3	c.732+518A>G		intron_variant	Intron 8 of 10		NP_542394.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERI2	ENST00000357967.9	c.1055A>G	p.Tyr352Cys	missense_variant	Exon 9 of 9	5	NM_001142725.2	ENSP00000350651.4

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64919 AN: 151926 Hom.: 16401 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.440

GnomAD2 exomes AF: 0.466 AC: 72989 AN: 156668 AF XY: 0.470

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.160

Gnomad FIN exome AF: 0.579

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.545 AC: 762501 AN: 1399282 Hom.: 216603 Cov.: 59 AF XY: 0.542 AC XY: 374279 AN XY: 690146

African (AFR) AF: 0.152 AC: 4792 AN: 31590

American (AMR) AF: 0.410 AC: 14641 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 10608 AN: 25176

East Asian (EAS) AF: 0.135 AC: 4836 AN: 35730

South Asian (SAS) AF: 0.410 AC: 32463 AN: 79232

European-Finnish (FIN) AF: 0.574 AC: 28308 AN: 49286

Middle Eastern (MID) AF: 0.408 AC: 2322 AN: 5698

European-Non Finnish (NFE) AF: 0.589 AC: 635792 AN: 1078860

Other (OTH) AF: 0.495 AC: 28739 AN: 58006

GnomAD4 genome AF: 0.427 AC: 64913 AN: 152044 Hom.: 16403 Cov.: 32 AF XY: 0.425 AC XY: 31586 AN XY: 74316

African (AFR) AF: 0.167 AC: 6931 AN: 41504

American (AMR) AF: 0.440 AC: 6721 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3472

East Asian (EAS) AF: 0.145 AC: 748 AN: 5176

South Asian (SAS) AF: 0.421 AC: 2030 AN: 4822

European-Finnish (FIN) AF: 0.574 AC: 6055 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39608 AN: 67932

Other (OTH) AF: 0.438 AC: 922 AN: 2104

Alfa AF: 0.527 Hom.: 80194

Bravo AF: 0.403

TwinsUK AF: 0.583 AC: 2161

ALSPAC AF: 0.584 AC: 2251

ESP6500AA AF: 0.177 AC: 245

ESP6500EA AF: 0.572 AC: 1820

ExAC AF: 0.439 AC: 10760

Asia WGS AF: 0.292 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.86
DEOGEN2	Benign	0.0038	.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.38	.;T;T
MetaRNN	Benign	0.000023	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	.;L;.
PhyloP100		-0.018
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.070	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.029
MPC		0.25
ClinPred		0.0087	T
GERP RS		-4.4
Varity_R		0.056
gMVP		0.21
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3213646; hg19: chr16-20810067; COSMIC: COSV55500475; COSMIC: COSV55500475;