rs2093266

Positions:

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

Variant summary

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

The NM_006215.4(SERPINA4):​c.650-520G>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_006215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA4	NM_006215.4	c.650-520G>A		intron_variant		ENST00000557004.6	NP_006206.2
SERPINA4	NM_001289032.2	c.761-520G>A		intron_variant			NP_001275961.1
SERPINA4	NM_001289033.2	c.650-520G>A		intron_variant			NP_001275962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA4	ENST00000557004.6	c.650-520G>A		intron_variant		1	NM_006215.4	ENSP00000450838	P1

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

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.137

Alfa AF: 0.125 Hom.: 406

Bravo AF: 0.152

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2093266; hg19: chr14-95032787;