rs17091162

Positions:

• chr14-94622895-C-A

Variant summary

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

The NM_001085.5(SERPINA3):​c.1068+404C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 309,622 control chromosomes in the GnomAD database, including 8,775 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 0.25 (4775 hom., cov: 33)
  • Exomes 𝑓: 0.22 (4000 hom.)
• Consequence: SERPINA3 NM_001085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

Genes affected

SERPINA3 (HGNC:16): (serpin family A member 3) 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. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]

ENSG00000273259 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINA3	NM_001085.5	c.1068+404C>A		intron_variant		ENST00000393078.5	NP_001076.2
SERPINA3	NM_001384672.1	c.1068+404C>A		intron_variant			NP_001371601.1
SERPINA3	NM_001384673.1	c.1068+404C>A		intron_variant			NP_001371602.1
SERPINA3	NM_001384674.1	c.1068+404C>A		intron_variant			NP_001371603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA3	ENST00000393078.5	c.1068+404C>A		intron_variant		1	NM_001085.5	ENSP00000376793.3
ENSG00000273259	ENST00000553947.1	n.*1894+404C>A		intron_variant		2		ENSP00000452367.2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37836 AN: 151968 Hom.: 4771 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.219 AC: 34500 AN: 157536 Hom.: 4000 AF XY: 0.218 AC XY: 18214 AN XY: 83418

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.249 AC: 37849 AN: 152086 Hom.: 4775 Cov.: 33 AF XY: 0.248 AC XY: 18470 AN XY: 74342

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.258

Alfa AF: 0.239 Hom.: 2827

Bravo AF: 0.254

Asia WGS AF: 0.207 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.41

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: rs17091162; hg19: chr14-95089232;