chr2-223995499-G-A

Variant names:

• chr2-223995499-G-A
• rs13396978
• NM_001136528.2:c.487+2616C>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+2616C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,106 control chromosomes in the GnomAD database, including 9,081 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 0.30 (9081 hom., cov: 33)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.487+2616C>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+2616C>T		intron_variant	Intron 3 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45369 AN: 151988 Hom.: 9058 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.299 AC: 45431 AN: 152106 Hom.: 9081 Cov.: 33 AF XY: 0.293 AC XY: 21784 AN XY: 74354

African (AFR) AF: 0.573 AC: 23737 AN: 41458

American (AMR) AF: 0.236 AC: 3606 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3472

East Asian (EAS) AF: 0.140 AC: 723 AN: 5174

South Asian (SAS) AF: 0.160 AC: 772 AN: 4824

European-Finnish (FIN) AF: 0.110 AC: 1168 AN: 10586

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

European-Non Finnish (NFE) AF: 0.199 AC: 13551 AN: 67990

Other (OTH) AF: 0.300 AC: 633 AN: 2108

Alfa AF: 0.225 Hom.: 7725

Bravo AF: 0.322

Asia WGS AF: 0.145 AC: 503 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	0.17
DANN	Benign	0.57
PhyloP100		-1.4
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: rs13396978; hg19: chr2-224860216;