rs6734100

Variant names:

• chr2-223977278-C-G
• rs6734100
• NM_001136528.2:c.1156+266G>C

Variant summary

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

The NM_001136528.2(SERPINE2):​c.1156+266G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,220 control chromosomes in the GnomAD database, including 1,057 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 0.11 (1057 hom., cov: 33)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.1156+266G>C		intron_variant	Intron 8 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.1156+266G>C		intron_variant	Intron 8 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16573 AN: 152102 Hom.: 1058 Cov.: 33

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.109 AC: 16565 AN: 152220 Hom.: 1057 Cov.: 33 AF XY: 0.108 AC XY: 8072 AN XY: 74412

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0985

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.109

Alfa AF: 0.116 Hom.: 120

Bravo AF: 0.106

Asia WGS AF: 0.140 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.1
DANN	Benign	0.38

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: rs6734100; hg19: chr2-224841995;