NM_001136528.2:c.555C>T

Variant names:

• chr2-223991933-G-A
• rs6712954
• NM_001136528.2:c.555C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001136528.2(SERPINE2):​c.555C>T​(p.Asn185Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,613,120 control chromosomes in the GnomAD database, including 7,155 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 0.12 (1521 hom., cov: 32)
  • Exomes 𝑓: 0.069 (5634 hom.)
• Consequence: SERPINE2 NM_001136528.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 19 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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.074 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 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.555C>T	p.Asn185Asn	synonymous	Exon 4 of 9	NP_001130000.1
	SERPINE2	NM_001136530.1		c.591C>T	p.Asn197Asn	synonymous	Exon 4 of 9	NP_001130002.1
	SERPINE2	NM_006216.4		c.555C>T	p.Asn185Asn	synonymous	Exon 4 of 9	NP_006207.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.555C>T	p.Asn185Asn	synonymous	Exon 4 of 9	ENSP00000386412.1
	SERPINE2	ENST00000258405.9	TSL:1	c.555C>T	p.Asn185Asn	synonymous	Exon 4 of 9	ENSP00000258405.4
	SERPINE2	ENST00000409840.7	TSL:1	c.555C>T	p.Asn185Asn	synonymous	Exon 5 of 10	ENSP00000386969.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17833 AN: 152094 Hom.: 1517 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.139

GnomAD2 exomes AF: 0.107 AC: 26810 AN: 250094 AF XY: 0.0962

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.0145

Gnomad NFE exome AF: 0.0566

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0692 AC: 101100 AN: 1460908 Hom.: 5634 Cov.: 32 AF XY: 0.0679 AC XY: 49371 AN XY: 726738

African (AFR) AF: 0.209 AC: 6986 AN: 33412

American (AMR) AF: 0.282 AC: 12557 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3696 AN: 26050

East Asian (EAS) AF: 0.156 AC: 6186 AN: 39684

South Asian (SAS) AF: 0.0565 AC: 4862 AN: 86122

European-Finnish (FIN) AF: 0.0163 AC: 871 AN: 53390

Middle Eastern (MID) AF: 0.166 AC: 959 AN: 5760

European-Non Finnish (NFE) AF: 0.0538 AC: 59790 AN: 1111598

Other (OTH) AF: 0.0860 AC: 5193 AN: 60366

GnomAD4 genome AF: 0.117 AC: 17859 AN: 152212 Hom.: 1521 Cov.: 32 AF XY: 0.118 AC XY: 8759 AN XY: 74416

African (AFR) AF: 0.207 AC: 8597 AN: 41492

American (AMR) AF: 0.221 AC: 3375 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3470

East Asian (EAS) AF: 0.161 AC: 832 AN: 5174

South Asian (SAS) AF: 0.0628 AC: 303 AN: 4824

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10616

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0554 AC: 3771 AN: 68018

Other (OTH) AF: 0.138 AC: 291 AN: 2114

Alfa AF: 0.100 Hom.: 1961

Bravo AF: 0.139

Asia WGS AF: 0.0940 AC: 326 AN: 3478

EpiCase AF: 0.0679

EpiControl AF: 0.0680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.4
DANN	Benign	0.78
PhyloP100		0.074
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6712954; hg19: chr2-224856650; COSMIC: COSV51457572;