rs17091162

Variant names:

• chr14-94622895-C-A
• rs17091162
• NM_001085.5:c.1068+404C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085.5. 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
	SERPINA3	NM_001085.5	MANE Select	c.1068+404C>A		intron	N/A	NP_001076.2
	SERPINA3	NM_001384672.1		c.1068+404C>A		intron	N/A	NP_001371601.1
	SERPINA3	NM_001384673.1		c.1068+404C>A		intron	N/A	NP_001371602.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA3	ENST00000393078.5	TSL:1 MANE Select	c.1068+404C>A		intron	N/A	ENSP00000376793.3
	SERPINA3	ENST00000393080.8	TSL:1	c.1068+404C>A		intron	N/A	ENSP00000376795.4
	SERPINA3	ENST00000482740.2	TSL:1	c.414+404C>A		intron	N/A	ENSP00000451119.1

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

African (AFR) AF: 0.300 AC: 1525 AN: 5084

American (AMR) AF: 0.234 AC: 1876 AN: 8000

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1243 AN: 3936

East Asian (EAS) AF: 0.144 AC: 1104 AN: 7660

South Asian (SAS) AF: 0.210 AC: 5531 AN: 26278

European-Finnish (FIN) AF: 0.198 AC: 1379 AN: 6966

Middle Eastern (MID) AF: 0.278 AC: 161 AN: 580

European-Non Finnish (NFE) AF: 0.218 AC: 19848 AN: 91064

Other (OTH) AF: 0.230 AC: 1833 AN: 7968

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

African (AFR) AF: 0.293 AC: 12160 AN: 41458

American (AMR) AF: 0.246 AC: 3763 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3468

East Asian (EAS) AF: 0.164 AC: 850 AN: 5174

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4822

European-Finnish (FIN) AF: 0.226 AC: 2395 AN: 10578

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15537 AN: 67972

Other (OTH) AF: 0.258 AC: 545 AN: 2116

Alfa AF: 0.239 Hom.: 9569

Bravo AF: 0.254

Asia WGS AF: 0.207 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.41
PhyloP100		0.27
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: rs17091162; hg19: chr14-95089232;