NM_001136528.2:c.-22-12811A>G

Variant names:

• chr2-224014733-T-C
• rs1371028
• NM_001136528.2:c.-22-12811A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):​c.-22-12811A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,226 control chromosomes in the GnomAD database, including 52,159 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 0.82 (52159 hom., cov: 33)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 7 publications found

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]

ENSG00000310283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-22-12811A>G		intron_variant	Intron 1 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-22-12811A>G		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125012 AN: 152108 Hom.: 52159 Cov.: 33

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.822 AC: 125056 AN: 152226 Hom.: 52159 Cov.: 33 AF XY: 0.818 AC XY: 60872 AN XY: 74420

African (AFR) AF: 0.698 AC: 28979 AN: 41512

American (AMR) AF: 0.825 AC: 12631 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3020 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2968 AN: 5158

South Asian (SAS) AF: 0.786 AC: 3790 AN: 4822

European-Finnish (FIN) AF: 0.874 AC: 9269 AN: 10610

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61673 AN: 68026

Other (OTH) AF: 0.842 AC: 1781 AN: 2114

Alfa AF: 0.844 Hom.: 9219

Bravo AF: 0.812

Asia WGS AF: 0.661 AC: 2302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.79
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1371028; hg19: chr2-224879450;