2-224035127-T-C

Variant names:

• chr2-224035127-T-C
• rs840088
• NM_001136528.2:c.-23+3972A>G

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+3972A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,884 control chromosomes in the GnomAD database, including 29,845 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 0.62 (29845 hom., cov: 30)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-23+3972A>G		intron_variant	Intron 1 of 8	ENST00000409304.6	NP_001130000.1
SERPINE2	NM_001136530.1	c.14+3363A>G		intron_variant	Intron 1 of 8		NP_001130002.1
SERPINE2	NM_006216.4	c.-23+3972A>G		intron_variant	Intron 1 of 8		NP_006207.1
SERPINE2	XM_005246641.3	c.14+3363A>G		intron_variant	Intron 1 of 8		XP_005246698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-23+3972A>G		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94517 AN: 151766 Hom.: 29830 Cov.: 30

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.623 AC: 94580 AN: 151884 Hom.: 29845 Cov.: 30 AF XY: 0.629 AC XY: 46689 AN XY: 74228

African (AFR) AF: 0.526 AC: 21772 AN: 41370

American (AMR) AF: 0.685 AC: 10467 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2248 AN: 3472

East Asian (EAS) AF: 0.582 AC: 3003 AN: 5158

South Asian (SAS) AF: 0.709 AC: 3413 AN: 4814

European-Finnish (FIN) AF: 0.726 AC: 7653 AN: 10546

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43972 AN: 67938

Other (OTH) AF: 0.610 AC: 1288 AN: 2110

Alfa AF: 0.644 Hom.: 20626

Bravo AF: 0.615

Asia WGS AF: 0.614 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.64
PhyloP100		0.10
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: rs840088; hg19: chr2-224899844;