NM_001136528.2:c.-22-11440T>C

Variant names:

• chr2-224013362-A-G
• rs1866152
• NM_001136528.2:c.-22-11440T>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.-22-11440T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,024 control chromosomes in the GnomAD database, including 49,780 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 0.80 (49780 hom., cov: 31)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136528.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	NM_001136528.2	MANE Select	c.-22-11440T>C		intron	N/A	NP_001130000.1
	SERPINE2	NM_001136530.1		c.15-11440T>C		intron	N/A	NP_001130002.1
	SERPINE2	NM_006216.4		c.-22-11440T>C		intron	N/A	NP_006207.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.-22-11440T>C		intron	N/A	ENSP00000386412.1
	SERPINE2	ENST00000258405.9	TSL:1	c.-22-11440T>C		intron	N/A	ENSP00000258405.4
	SERPINE2	ENST00000409840.7	TSL:1	c.-22-11440T>C		intron	N/A	ENSP00000386969.3

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121579 AN: 151906 Hom.: 49786 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.800 AC: 121610 AN: 152024 Hom.: 49780 Cov.: 31 AF XY: 0.796 AC XY: 59186 AN XY: 74312

African (AFR) AF: 0.637 AC: 26384 AN: 41416

American (AMR) AF: 0.809 AC: 12365 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2967 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2949 AN: 5130

South Asian (SAS) AF: 0.781 AC: 3759 AN: 4812

European-Finnish (FIN) AF: 0.874 AC: 9247 AN: 10586

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61275 AN: 68010

Other (OTH) AF: 0.819 AC: 1732 AN: 2114

Alfa AF: 0.854 Hom.: 7730

Bravo AF: 0.787

Asia WGS AF: 0.656 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.43
PhyloP100		-1.5
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: rs1866152; hg19: chr2-224878079;