rs2093266

Variant names:

• chr14-94566450-G-A
• rs2093266
• NM_006215.4:c.650-520G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-94566450-G-A
• chr14-94566450-G-T

Variant summary

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

The NM_001289032.2(SERPINA4):​c.761-520G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,078 control chromosomes in the GnomAD database, including 1,794 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 0.15 (1794 hom., cov: 32)
• Consequence: SERPINA4 NM_001289032.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 12 publications found

Genes affected

SERPINA4 (HGNC:8948): (serpin family A member 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Located in extracellular exosome. Biomarker of diabetic retinopathy. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA5 (HGNC:8723): (serpin family A member 5) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. This family member is a glycoprotein that can inhibit several serine proteases, including protein C and various plasminogen activators and kallikreins, and it thus plays diverse roles in hemostasis and thrombosis in multiple organs. [provided by RefSeq, Aug 2012]

ENSG00000294537 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289032.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA4	NM_006215.4	MANE Select	c.650-520G>A		intron	N/A	NP_006206.2
	SERPINA4	NM_001289032.2		c.761-520G>A		intron	N/A	NP_001275961.1
	SERPINA4	NM_001289033.2		c.650-520G>A		intron	N/A	NP_001275962.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA4	ENST00000557004.6	TSL:1 MANE Select	c.650-520G>A		intron	N/A	ENSP00000450838.1
	SERPINA4	ENST00000298841.5	TSL:1	c.650-520G>A		intron	N/A	ENSP00000298841.5
	SERPINA4	ENST00000555095.5	TSL:1	c.650-520G>A		intron	N/A	ENSP00000451172.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22103 AN: 151960 Hom.: 1785 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.146 AC: 22133 AN: 152078 Hom.: 1794 Cov.: 32 AF XY: 0.144 AC XY: 10740 AN XY: 74336

African (AFR) AF: 0.221 AC: 9157 AN: 41454

American (AMR) AF: 0.165 AC: 2531 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3470

East Asian (EAS) AF: 0.137 AC: 707 AN: 5166

South Asian (SAS) AF: 0.167 AC: 806 AN: 4814

European-Finnish (FIN) AF: 0.102 AC: 1073 AN: 10560

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7343 AN: 68006

Other (OTH) AF: 0.137 AC: 289 AN: 2106

Alfa AF: 0.128 Hom.: 517

Bravo AF: 0.152

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		0.41
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: rs2093266; hg19: chr14-95032787;