2-223980147-A-G

Variant names:

• chr2-223980147-A-G
• rs33916072
• NM_001136528.2:c.1072+164T>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.1072+164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 553,892 control chromosomes in the GnomAD database, including 54,708 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 0.38 (12545 hom., cov: 33)
  • Exomes 𝑓: 0.45 (42163 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.1072+164T>C		intron_variant	Intron 7 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.1072+164T>C		intron_variant	Intron 7 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57892 AN: 152054 Hom.: 12548 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.447 AC: 179640 AN: 401720 Hom.: 42163 Cov.: 5 AF XY: 0.448 AC XY: 94481 AN XY: 210984

African (AFR) AF: 0.171 AC: 1938 AN: 11320

American (AMR) AF: 0.406 AC: 6486 AN: 15994

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 3954 AN: 12038

East Asian (EAS) AF: 0.242 AC: 6843 AN: 28294

South Asian (SAS) AF: 0.471 AC: 16092 AN: 34154

European-Finnish (FIN) AF: 0.548 AC: 19599 AN: 35766

Middle Eastern (MID) AF: 0.352 AC: 621 AN: 1762

European-Non Finnish (NFE) AF: 0.478 AC: 114411 AN: 239360

Other (OTH) AF: 0.421 AC: 9696 AN: 23032

GnomAD4 genome AF: 0.381 AC: 57904 AN: 152172 Hom.: 12545 Cov.: 33 AF XY: 0.384 AC XY: 28554 AN XY: 74404

African (AFR) AF: 0.171 AC: 7092 AN: 41540

American (AMR) AF: 0.398 AC: 6078 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1125 AN: 3468

East Asian (EAS) AF: 0.247 AC: 1281 AN: 5180

South Asian (SAS) AF: 0.474 AC: 2289 AN: 4828

European-Finnish (FIN) AF: 0.561 AC: 5928 AN: 10576

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32867 AN: 67984

Other (OTH) AF: 0.376 AC: 791 AN: 2106

Alfa AF: 0.424 Hom.: 1807

Bravo AF: 0.355

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.82
PhyloP100		-0.24
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: rs33916072; hg19: chr2-224844864; COSMIC: COSV51459997; COSMIC: COSV51459997;