rs1371029

Variant names:

• chr2-224023756-A-G
• rs1371029
• NM_001136528.2:c.-23+15343T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):​c.-23+15343T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 152,308 control chromosomes in the GnomAD database, including 68,306 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 0.94 (68306 hom., cov: 33)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638
• Publications: 0 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]

ENSG00000310283 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-23+15343T>C		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.-23+15343T>C		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143776 AN: 152192 Hom.: 68273 Cov.: 33

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.945 AC: 143864 AN: 152308 Hom.: 68306 Cov.: 33 AF XY: 0.945 AC XY: 70358 AN XY: 74492

African (AFR) AF: 0.858 AC: 35627 AN: 41540

American (AMR) AF: 0.970 AC: 14848 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3430 AN: 3470

East Asian (EAS) AF: 0.781 AC: 4051 AN: 5184

South Asian (SAS) AF: 0.937 AC: 4524 AN: 4828

European-Finnish (FIN) AF: 0.997 AC: 10599 AN: 10630

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67593 AN: 68036

Other (OTH) AF: 0.949 AC: 2006 AN: 2114

Alfa AF: 0.970 Hom.: 8901

Bravo AF: 0.937

Asia WGS AF: 0.820 AC: 2853 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	5.4
DANN	Benign	0.83
PhyloP100		0.64
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: rs1371029; hg19: chr2-224888473;