rs9810473

Positions:

• chr3-167442192-A-G

Variant summary

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

The NM_006217.6(SERPINI2):​c.1142-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,530,250 control chromosomes in the GnomAD database, including 14,723 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (4065 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10658 hom.)
• Consequence: SERPINI2 NM_006217.6 splice_region, intron
• Scores: Splicing: ADA: 0.000008634
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845

Genes affected

SERPINI2 (HGNC:8945): (serpin family I member 2) The gene encodes a member of a family of proteins that acts as inhibitors of serine proteases. These proteins function in the regulation of a variety of physiological processes, including coagulation, fibrinolysis, development, malignancy, and inflammation. Expression of the encoded protein may be downregulated during pancreatic carcinogenesis. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]

SERPINI2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINI2	NM_006217.6	c.1142-7T>C		splice_region_variant, intron_variant		ENST00000264677.9	NP_006208.1
SERPINI2	NM_001012303.3	c.1142-7T>C		splice_region_variant, intron_variant			NP_001012303.2
SERPINI2	NM_001394327.1	c.1142-7T>C		splice_region_variant, intron_variant			NP_001381256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINI2	ENST00000264677.9	c.1142-7T>C		splice_region_variant, intron_variant		1	NM_006217.6	ENSP00000264677.4
SERPINI2	ENST00000461846.5	c.1142-7T>C		splice_region_variant, intron_variant		1		ENSP00000417692.1
SERPINI2	ENST00000471111.5	c.1142-7T>C		splice_region_variant, intron_variant		1		ENSP00000419407.1
SERPINI2	ENST00000495108.1	n.615-7T>C		splice_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 28795 AN: 145182 Hom.: 4051 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.0948

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0902

Gnomad OTH AF: 0.164

GnomAD3 exomes AF: 0.175 AC: 29142 AN: 166432 Hom.: 2815 AF XY: 0.161 AC XY: 14613 AN XY: 90986

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.334

Gnomad SAS exome AF: 0.0995

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.106 AC: 147121 AN: 1384972 Hom.: 10658 Cov.: 25 AF XY: 0.104 AC XY: 71993 AN XY: 689330

Gnomad4 AFR exome AF: 0.399

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.0801

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0875

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.199 AC: 28857 AN: 145278 Hom.: 4065 Cov.: 32 AF XY: 0.196 AC XY: 13913 AN XY: 71052

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.0943

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0903

Gnomad4 OTH AF: 0.169

Alfa AF: 0.119 Hom.: 419

Bravo AF: 0.211

Asia WGS AF: 0.211 AC: 726 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000086
dbscSNV1_RF	Benign	0.0020
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: rs9810473; hg19: chr3-167159980; COSMIC: COSV52986783;