rs3948261

Variant names:

• chr2-224005175-C-T
• rs3948261
• NM_001136528.2:c.-22-3253G>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.-22-3253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 148,088 control chromosomes in the GnomAD database, including 35,244 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 0.69 (35244 hom., cov: 25)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 1 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-22-3253G>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.-22-3253G>A		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 101577 AN: 148004 Hom.: 35258 Cov.: 25

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.686 AC: 101586 AN: 148088 Hom.: 35244 Cov.: 25 AF XY: 0.688 AC XY: 49638 AN XY: 72106

African (AFR) AF: 0.562 AC: 22457 AN: 39952

American (AMR) AF: 0.707 AC: 10473 AN: 14816

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2461 AN: 3456

East Asian (EAS) AF: 0.587 AC: 2920 AN: 4976

South Asian (SAS) AF: 0.740 AC: 3510 AN: 4746

European-Finnish (FIN) AF: 0.753 AC: 7221 AN: 9592

Middle Eastern (MID) AF: 0.654 AC: 183 AN: 280

European-Non Finnish (NFE) AF: 0.749 AC: 50414 AN: 67346

Other (OTH) AF: 0.702 AC: 1428 AN: 2034

Alfa AF: 0.689 Hom.: 4027

Bravo AF: 0.671

Asia WGS AF: 0.611 AC: 2124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.6
DANN	Benign	0.73
PhyloP100		-1.6
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: rs3948261; hg19: chr2-224869892;