rs12476888

Variant names:

• chr2-224029204-C-T
• rs12476888
• NM_001136528.2:c.-23+9895G>A

Variant summary

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

The NM_001136528.2(SERPINE2):​c.-23+9895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,070 control chromosomes in the GnomAD database, including 16,859 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 0.44 (16859 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-23+9895G>A		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.-23+9895G>A		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66962 AN: 151952 Hom.: 16861 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.440 AC: 66965 AN: 152070 Hom.: 16859 Cov.: 32 AF XY: 0.446 AC XY: 33121 AN XY: 74336

African (AFR) AF: 0.181 AC: 7528 AN: 41504

American (AMR) AF: 0.516 AC: 7879 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1835 AN: 3468

East Asian (EAS) AF: 0.310 AC: 1609 AN: 5182

South Asian (SAS) AF: 0.544 AC: 2619 AN: 4818

European-Finnish (FIN) AF: 0.601 AC: 6336 AN: 10546

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37657 AN: 67962

Other (OTH) AF: 0.469 AC: 990 AN: 2110

Alfa AF: 0.515 Hom.: 25744

Bravo AF: 0.421

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.1
DANN	Benign	0.39
PhyloP100		0.54
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: rs12476888; hg19: chr2-224893921;