3-167442192-A-G

Variant names:

• chr3-167442192-A-G
• rs9810473
• NM_006217.6:c.1142-7T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SERPINI2	NM_006217.6	c.1142-7T>C		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000264677.9	NP_006208.1
SERPINI2	NM_001012303.3	c.1142-7T>C		splice_region_variant, intron_variant	Intron 9 of 9		NP_001012303.2
SERPINI2	NM_001394327.1	c.1142-7T>C		splice_region_variant, intron_variant	Intron 9 of 9		NP_001381256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINI2	ENST00000264677.9	c.1142-7T>C		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_006217.6	ENSP00000264677.4
SERPINI2	ENST00000461846.5	c.1142-7T>C		splice_region_variant, intron_variant	Intron 8 of 8	1		ENSP00000417692.1
SERPINI2	ENST00000471111.5	c.1142-7T>C		splice_region_variant, intron_variant	Intron 7 of 7	1		ENSP00000419407.1
SERPINI2	ENST00000495108.1	n.615-7T>C		splice_region_variant, intron_variant	Intron 1 of 1	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

GnomAD2 exomes AF: 0.175 AC: 29142 AN: 166432 AF XY: 0.161

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 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

African (AFR) AF: 0.399 AC: 11788 AN: 29544

American (AMR) AF: 0.230 AC: 7441 AN: 32348

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 2801 AN: 23810

East Asian (EAS) AF: 0.322 AC: 12141 AN: 37734

South Asian (SAS) AF: 0.0801 AC: 6018 AN: 75142

European-Finnish (FIN) AF: 0.102 AC: 5004 AN: 49150

Middle Eastern (MID) AF: 0.119 AC: 620 AN: 5220

European-Non Finnish (NFE) AF: 0.0875 AC: 94106 AN: 1075004

Other (OTH) AF: 0.126 AC: 7202 AN: 57020

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

African (AFR) AF: 0.445 AC: 16178 AN: 36370

American (AMR) AF: 0.179 AC: 2646 AN: 14742

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3454

East Asian (EAS) AF: 0.307 AC: 1509 AN: 4908

South Asian (SAS) AF: 0.0943 AC: 446 AN: 4730

European-Finnish (FIN) AF: 0.102 AC: 1058 AN: 10406

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0903 AC: 6090 AN: 67474

Other (OTH) AF: 0.169 AC: 337 AN: 1994

Alfa AF: 0.126 Hom.: 762

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
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9810473; hg19: chr3-167159980; COSMIC: COSV52986783;