rs729631

Variant names:

• chr2-223980202-C-A
• rs729631
• NM_001136528.2:c.1072+109G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-223980202-C-A
• chr2-223980202-C-G
• chr2-223980202-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001136528.2(SERPINE2):​c.1072+109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 887,296 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00087 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000087 (0 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 11 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 132 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.1072+109G>T		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+109G>T		intron_variant	Intron 7 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.000861 AC: 131 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000871 AC: 64 AN: 735092 Hom.: 0 Cov.: 10 AF XY: 0.0000752 AC XY: 29 AN XY: 385756

African (AFR) AF: 0.00252 AC: 48 AN: 19010

American (AMR) AF: 0.000238 AC: 9 AN: 37804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19164

East Asian (EAS) AF: 0.00 AC: 0 AN: 33742

South Asian (SAS) AF: 0.0000313 AC: 2 AN: 63824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 473356

Other (OTH) AF: 0.000140 AC: 5 AN: 35768

GnomAD4 genome AF: 0.000867 AC: 132 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.000887 AC XY: 66 AN XY: 74420

African (AFR) AF: 0.00308 AC: 128 AN: 41512

American (AMR) AF: 0.000261 AC: 4 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 2360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.12
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs729631; hg19: chr2-224844919;