rs36034130

Positions:

• chr2-223997983-C-A
• chr2-223997983-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):​c.487+132G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 691,978 control chromosomes in the GnomAD database, including 4,593 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 (1326 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3267 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.487+132G>T		intron_variant		ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.487+132G>T		intron_variant		1	NM_001136528.2	ENSP00000386412	A1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18559 AN: 152070 Hom.: 1321 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.0896

GnomAD4 exome AF: 0.102 AC: 54996 AN: 539790 Hom.: 3267 AF XY: 0.105 AC XY: 30070 AN XY: 285748

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.0189

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.0921

Gnomad4 OTH exome AF: 0.0979

GnomAD4 genome AF: 0.122 AC: 18597 AN: 152188 Hom.: 1326 Cov.: 32 AF XY: 0.123 AC XY: 9169 AN XY: 74422

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0932

Gnomad4 OTH AF: 0.0882

Alfa AF: 0.0771 Hom.: 141

Bravo AF: 0.124

Asia WGS AF: 0.0810 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.17
DANN	Benign	0.68

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: rs36034130; hg19: chr2-224862700;