rs1020118

Positions:

• chr2-224031721-A-G
• chr2-224031721-A-T

Variant summary

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

The NM_001136528.2(SERPINE2):​c.-23+7378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 149,612 control chromosomes in the GnomAD database, including 31,874 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 0.65 (31874 hom., cov: 26)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-23+7378T>C		intron_variant		ENST00000409304.6	NP_001130000.1
SERPINE2	NM_001136530.1	c.14+6769T>C		intron_variant			NP_001130002.1
SERPINE2	NM_006216.4	c.-23+7378T>C		intron_variant			NP_006207.1
SERPINE2	XM_005246641.3	c.14+6769T>C		intron_variant			XP_005246698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-23+7378T>C		intron_variant		1	NM_001136528.2	ENSP00000386412	A1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 97276 AN: 149488 Hom.: 31851 Cov.: 26

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.651 AC: 97351 AN: 149612 Hom.: 31874 Cov.: 26 AF XY: 0.656 AC XY: 47765 AN XY: 72856

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.636

Alfa AF: 0.670 Hom.: 5955

Bravo AF: 0.649

Asia WGS AF: 0.629 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.53

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: rs1020118; hg19: chr2-224896438;