rs2070777

chr14-94568005-T-A

Variant summary

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

The NM_006215.4(SERPINA4):c.924-124T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 920,980 control chromosomes in the GnomAD database, including 68,632 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 0.41 (13319 hom., cov: 32)
  • Exomes 𝑓: 0.37 (55313 hom.)
• Consequence: SERPINA4 NM_006215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA4	NM_006215.4	c.924-124T>A		intron_variant		ENST00000557004.6
SERPINA4	NM_001289032.2	c.1035-124T>A		intron_variant
SERPINA4	NM_001289033.2	c.924-124T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA4	ENST00000557004.6	c.924-124T>A		intron_variant		1	NM_006215.4	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62559 AN: 151900 Hom.: 13289 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.373 AC: 286951 AN: 768958 Hom.: 55313 AF XY: 0.378 AC XY: 150223 AN XY: 397388

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.412 AC: 62648 AN: 152022 Hom.: 13319 Cov.: 32 AF XY: 0.415 AC XY: 30815 AN XY: 74288

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.426

Alfa AF: 0.387 Hom.: 1428

Bravo AF: 0.408

Asia WGS AF: 0.497 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.62
Dann	Benign	0.65

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: rs2070777; hg19: chr14-95034342;