rs7579646

Variant names:

• chr2-224035979-G-A
• rs7579646
• NM_001136528.2:c.-23+3120C>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.-23+3120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 122,672 control chromosomes in the GnomAD database, including 2,838 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 0.24 (2838 hom., cov: 33)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591
• Publications: 7 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]

ENSG00000310283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-23+3120C>T		intron_variant	Intron 1 of 8	ENST00000409304.6	NP_001130000.1
SERPINE2	NM_001136530.1	c.14+2511C>T		intron_variant	Intron 1 of 8		NP_001130002.1
SERPINE2	NM_006216.4	c.-23+3120C>T		intron_variant	Intron 1 of 8		NP_006207.1
SERPINE2	XM_005246641.3	c.14+2511C>T		intron_variant	Intron 1 of 8		XP_005246698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-23+3120C>T		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 28908 AN: 122570 Hom.: 2838 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.265

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.236 AC: 28912 AN: 122672 Hom.: 2838 Cov.: 33 AF XY: 0.236 AC XY: 13929 AN XY: 59010

African (AFR) AF: 0.231 AC: 8209 AN: 35596

American (AMR) AF: 0.246 AC: 2668 AN: 10860

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 815 AN: 2892

East Asian (EAS) AF: 0.222 AC: 954 AN: 4290

South Asian (SAS) AF: 0.250 AC: 784 AN: 3142

European-Finnish (FIN) AF: 0.185 AC: 1350 AN: 7304

Middle Eastern (MID) AF: 0.268 AC: 67 AN: 250

European-Non Finnish (NFE) AF: 0.241 AC: 13478 AN: 55920

Other (OTH) AF: 0.256 AC: 432 AN: 1690

Alfa AF: 0.181 Hom.: 420

Bravo AF: 0.194

Asia WGS AF: 0.131 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.64
PhyloP100		0.59
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: rs7579646; hg19: chr2-224900696; COSMIC: COSV51458738; COSMIC: COSV51458738;