rs6436449

chr2-223983616-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):c.885-835G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 151,458 control chromosomes in the GnomAD database, including 51,042 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 (51042 hom., cov: 27)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.885-835G>A		intron_variant		ENST00000409304.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.885-835G>A		intron_variant		1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124139 AN: 151340 Hom.: 51003 Cov.: 27

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.820 AC: 124233 AN: 151458 Hom.: 51042 Cov.: 27 AF XY: 0.819 AC XY: 60595 AN XY: 74002

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.813

Alfa AF: 0.836 Hom.: 21558

Bravo AF: 0.819

Asia WGS AF: 0.721 AC: 2507 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.17
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs6436449; hg19: chr2-224848333;