rs6747096

Positions:

• chr2-223998125-A-G

Variant summary

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

The NM_001136528.2(SERPINE2):​c.477T>C​(p.Asn159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,612,994 control chromosomes in the GnomAD database, including 38,675 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 0.26 (6405 hom., cov: 33)
  • Exomes 𝑓: 0.20 (32270 hom.)
• Consequence: SERPINE2 NM_001136528.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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=-0.63).
• BP7: Synonymous conserved (PhyloP=0.338 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.477T>C	p.Asn159=	synonymous_variant	3/9	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.477T>C	p.Asn159=	synonymous_variant	3/9	1	NM_001136528.2	ENSP00000386412	A1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39996 AN: 152038 Hom.: 6391 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.267

GnomAD3 exomes AF: 0.197 AC: 49459 AN: 251120 Hom.: 5792 AF XY: 0.196 AC XY: 26624 AN XY: 135716

Gnomad AFR exome AF: 0.456

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.135

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.203 AC: 295851 AN: 1460838 Hom.: 32270 Cov.: 32 AF XY: 0.202 AC XY: 146815 AN XY: 726750

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.263 AC: 40043 AN: 152156 Hom.: 6405 Cov.: 33 AF XY: 0.258 AC XY: 19187 AN XY: 74394

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.264

Alfa AF: 0.218 Hom.: 6320

Bravo AF: 0.282

Asia WGS AF: 0.138 AC: 479 AN: 3478

EpiCase AF: 0.213

EpiControl AF: 0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.4
DANN	Benign	0.53

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: rs12457; hg19: chr2-224862842; COSMIC: COSV51456455; COSMIC: COSV51456455;