rs10191694

Variant names:

• chr2-223992549-A-C
• rs10191694
• NM_001136528.2:c.488-549T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-223992549-A-C
• chr2-223992549-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):​c.488-549T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,926 control chromosomes in the GnomAD database, including 29,703 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 0.62 (29703 hom., cov: 31)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.704 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.488-549T>G		intron	N/A	NP_001130000.1
	SERPINE2	NM_001136530.1		c.524-549T>G		intron	N/A	NP_001130002.1
	SERPINE2	NM_006216.4		c.488-549T>G		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.488-549T>G		intron	N/A	ENSP00000386412.1
	SERPINE2	ENST00000258405.9	TSL:1	c.488-549T>G		intron	N/A	ENSP00000258405.4
	SERPINE2	ENST00000409840.7	TSL:1	c.488-549T>G		intron	N/A	ENSP00000386969.3

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94225 AN: 151808 Hom.: 29687 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.621 AC: 94275 AN: 151926 Hom.: 29703 Cov.: 31 AF XY: 0.618 AC XY: 45875 AN XY: 74248

African (AFR) AF: 0.541 AC: 22430 AN: 41426

American (AMR) AF: 0.715 AC: 10923 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1948 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2242 AN: 5164

South Asian (SAS) AF: 0.584 AC: 2811 AN: 4816

European-Finnish (FIN) AF: 0.618 AC: 6492 AN: 10504

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45379 AN: 67946

Other (OTH) AF: 0.624 AC: 1319 AN: 2114

Alfa AF: 0.650 Hom.: 143101

Bravo AF: 0.625

Asia WGS AF: 0.480 AC: 1668 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.80
PhyloP100		-0.11
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: rs10191694; hg19: chr2-224857266;