2-223998104-C-T

Variant names:

• chr2-223998104-C-T
• rs3795879
• NM_001136528.2:c.487+11G>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.487+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,594,248 control chromosomes in the GnomAD database, including 42,789 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 0.29 (8287 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34502 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• Publications: 16 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]

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 (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.487+11G>A		intron_variant	Intron 3 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.487+11G>A		intron_variant	Intron 3 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44175 AN: 151972 Hom.: 8267 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.303

GnomAD2 exomes AF: 0.208 AC: 51987 AN: 250398 AF XY: 0.205

Gnomad AFR exome AF: 0.535

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.274

Gnomad EAS exome AF: 0.134

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.208 AC: 300545 AN: 1442158 Hom.: 34502 Cov.: 28 AF XY: 0.208 AC XY: 149366 AN XY: 718688

African (AFR) AF: 0.543 AC: 17871 AN: 32926

American (AMR) AF: 0.165 AC: 7386 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 7139 AN: 25996

East Asian (EAS) AF: 0.156 AC: 6189 AN: 39616

South Asian (SAS) AF: 0.177 AC: 15184 AN: 85824

European-Finnish (FIN) AF: 0.115 AC: 6134 AN: 53324

Middle Eastern (MID) AF: 0.329 AC: 1885 AN: 5730

European-Non Finnish (NFE) AF: 0.206 AC: 225038 AN: 1094376

Other (OTH) AF: 0.230 AC: 13719 AN: 59728

GnomAD4 genome AF: 0.291 AC: 44232 AN: 152090 Hom.: 8287 Cov.: 32 AF XY: 0.285 AC XY: 21198 AN XY: 74344

African (AFR) AF: 0.534 AC: 22155 AN: 41466

American (AMR) AF: 0.234 AC: 3573 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3472

East Asian (EAS) AF: 0.140 AC: 721 AN: 5168

South Asian (SAS) AF: 0.170 AC: 817 AN: 4810

European-Finnish (FIN) AF: 0.111 AC: 1180 AN: 10590

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13904 AN: 67988

Other (OTH) AF: 0.299 AC: 632 AN: 2114

Alfa AF: 0.280 Hom.: 1769

Bravo AF: 0.313

Asia WGS AF: 0.145 AC: 502 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	0.0030
DANN	Benign	0.54
PhyloP100		-2.2
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: rs3795879; hg19: chr2-224862821; COSMIC: COSV51456445; COSMIC: COSV51456445;