rs1530021

Positions:

• chr2-224006519-A-G

Variant summary

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

The NM_001136528.2(SERPINE2):​c.-22-4597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 151,968 control chromosomes in the GnomAD database, including 35,742 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 0.68 (35742 hom., cov: 31)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-22-4597T>C		intron_variant		ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-22-4597T>C		intron_variant		1	NM_001136528.2	ENSP00000386412	A1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103476 AN: 151850 Hom.: 35751 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.681 AC: 103505 AN: 151968 Hom.: 35742 Cov.: 31 AF XY: 0.683 AC XY: 50732 AN XY: 74256

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.692

Alfa AF: 0.692 Hom.: 4566

Bravo AF: 0.671

Asia WGS AF: 0.613 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.35

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: rs1530021; hg19: chr2-224871236;