rs1530020

Positions:

• chr2-224006653-C-A
• chr2-224006653-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.-22-4731G>T 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 152,040 control chromosomes in the GnomAD database, including 35,756 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 (35756 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815

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=-0.85).
• 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	UniProt
SERPINE2	NM_001136528.2	c.-22-4731G>T		intron_variant		ENST00000409304.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-22-4731G>T		intron_variant		1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103508 AN: 151922 Hom.: 35765 Cov.: 32

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: 0.736

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.681 AC: 103537 AN: 152040 Hom.: 35756 Cov.: 32 AF XY: 0.683 AC XY: 50773 AN XY: 74322

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.693

Alfa AF: 0.590 Hom.: 1684

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	-0.85
CADD	Benign	4.0
DANN	Benign	0.66

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: rs1530020; hg19: chr2-224871370;