rs7590948

Positions:

• chr2-224008973-G-A

Variant summary

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

The NM_001136528.2(SERPINE2):​c.-22-7051C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,848 control chromosomes in the GnomAD database, including 16,235 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 0.43 (16235 hom., cov: 31)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783

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]

LOC124907990 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.-22-7051C>T		intron_variant		ENST00000409304.6
LOC124907990	XR_007088102.1	n.97G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-22-7051C>T		intron_variant		1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64740 AN: 151730 Hom.: 16246 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.426 AC: 64733 AN: 151848 Hom.: 16235 Cov.: 31 AF XY: 0.433 AC XY: 32088 AN XY: 74158

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.441

Alfa AF: 0.514 Hom.: 22355

Bravo AF: 0.402

Asia WGS AF: 0.468 AC: 1630 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	3.6
DANN	Benign	0.56

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: rs7590948; hg19: chr2-224873690;