rs12138

chr2-224001670-G-Achr2-224001670-G-Cchr2-224001670-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001136528.2(SERPINE2):c.231C>T(p.Leu77=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,844 control chromosomes in the GnomAD database, including 13,259 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 (2006 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11253 hom.)
• Consequence: SERPINE2 NM_001136528.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

SERPINE2 (HGNC:8951): (serpin family E member 2) This gene encodes a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. Thrombin, urokinase, plasmin and trypsin are among the proteases that this family member can inhibit. This gene is a susceptibility gene for chronic obstructive pulmonary disease and for emphysema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=1.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.231C>T	p.Leu77=	synonymous_variant	2/9	ENST00000409304.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.231C>T	p.Leu77=	synonymous_variant	2/9	1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22937 AN: 152060 Hom.: 1997 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.121

GnomAD3 exomes AF: 0.148 AC: 37047 AN: 250882 Hom.: 3111 AF XY: 0.146 AC XY: 19749 AN XY: 135610

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.208

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0998

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.116 AC: 169562 AN: 1461666 Hom.: 11253 Cov.: 33 AF XY: 0.119 AC XY: 86234 AN XY: 727142

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0975

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.151 AC: 22987 AN: 152178 Hom.: 2006 Cov.: 32 AF XY: 0.153 AC XY: 11407 AN XY: 74394

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.120

Alfa AF: 0.106 Hom.: 941

Bravo AF: 0.155

Asia WGS AF: 0.195 AC: 678 AN: 3478

EpiCase AF: 0.0976

EpiControl AF: 0.0990

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	6.4
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs12138; hg19: chr2-224866387; COSMIC: COSV51457499; COSMIC: COSV51457499;