rs6712954

chr2-223991933-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001136528.2(SERPINE2):c.555C>T(p.Asn185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,613,120 control chromosomes in the GnomAD database, including 7,155 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 0.12 (1521 hom., cov: 32)
  • Exomes 𝑓: 0.069 (5634 hom.)
• Consequence: SERPINE2 NM_001136528.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.074 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.555C>T	p.Asn185=	synonymous_variant	4/9	ENST00000409304.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.555C>T	p.Asn185=	synonymous_variant	4/9	1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17833 AN: 152094 Hom.: 1517 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.139

GnomAD3 exomes AF: 0.107 AC: 26810 AN: 250094 Hom.: 2586 AF XY: 0.0962 AC XY: 13005 AN XY: 135156

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.0527

Gnomad FIN exome AF: 0.0145

Gnomad NFE exome AF: 0.0566

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0692 AC: 101100 AN: 1460908 Hom.: 5634 Cov.: 32 AF XY: 0.0679 AC XY: 49371 AN XY: 726738

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.0565

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.0538

Gnomad4 OTH exome AF: 0.0860

GnomAD4 genome AF: 0.117 AC: 17859 AN: 152212 Hom.: 1521 Cov.: 32 AF XY: 0.118 AC XY: 8759 AN XY: 74416

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0554

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0895 Hom.: 875

Bravo AF: 0.139

Asia WGS AF: 0.0940 AC: 326 AN: 3478

EpiCase AF: 0.0679

EpiControl AF: 0.0680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	2.4
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6712954; hg19: chr2-224856650; COSMIC: COSV51457572;