NM_001136528.2:c.-22-14167A>G

Variant names:

• chr2-224016089-T-C
• rs2083122
• NM_001136528.2:c.-22-14167A>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.-22-14167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,340 control chromosomes in the GnomAD database, including 68,222 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 (68222 hom., cov: 34)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-22-14167A>G		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.-22-14167A>G		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143714 AN: 152222 Hom.: 68189 Cov.: 34

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.954

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

GnomAD4 genome AF: 0.944 AC: 143803 AN: 152340 Hom.: 68222 Cov.: 34 AF XY: 0.944 AC XY: 70313 AN XY: 74502

African (AFR) AF: 0.859 AC: 35679 AN: 41550

American (AMR) AF: 0.967 AC: 14800 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3426 AN: 3468

East Asian (EAS) AF: 0.782 AC: 4053 AN: 5186

South Asian (SAS) AF: 0.936 AC: 4523 AN: 4830

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

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67536 AN: 68050

Other (OTH) AF: 0.946 AC: 2000 AN: 2114

Alfa AF: 0.981 Hom.: 3585

Bravo AF: 0.936

Asia WGS AF: 0.820 AC: 2855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		-0.31
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: rs2083122; hg19: chr2-224880806;