rs11695803

Variant names:

• chr2-223996444-G-A
• rs11695803
• NM_001136528.2:c.487+1671C>T

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+1671C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,088 control chromosomes in the GnomAD database, including 1,316 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 0.12 (1316 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.487+1671C>T		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+1671C>T		intron_variant	Intron 3 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18520 AN: 151970 Hom.: 1311 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.0896

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

GnomAD4 genome AF: 0.122 AC: 18558 AN: 152088 Hom.: 1316 Cov.: 32 AF XY: 0.123 AC XY: 9130 AN XY: 74330

African (AFR) AF: 0.177 AC: 7340 AN: 41478

American (AMR) AF: 0.127 AC: 1934 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3468

East Asian (EAS) AF: 0.0244 AC: 126 AN: 5174

South Asian (SAS) AF: 0.161 AC: 771 AN: 4798

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0932 AC: 6338 AN: 67988

Other (OTH) AF: 0.0882 AC: 186 AN: 2110

Alfa AF: 0.113 Hom.: 902

Bravo AF: 0.123

Asia WGS AF: 0.0830 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.58
PhyloP100		0.52
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: rs11695803; hg19: chr2-224861161;