rs2069990

Positions:

• chr14-94592277-G-A
• chr14-94592277-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000624.6(SERPINA5):​c.*38G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,585,086 control chromosomes in the GnomAD database, including 549 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 0.022 (38 hom., cov: 33)
  • Exomes 𝑓: 0.024 (511 hom.)
• Consequence: SERPINA5 NM_000624.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799

Genes affected

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=-0.82).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0222 (3378/152310) while in subpopulation SAS AF= 0.0321 (155/4828). AF 95% confidence interval is 0.028. There are 38 homozygotes in gnomad4. There are 1706 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA5	NM_000624.6	c.*38G>A		3_prime_UTR_variant	6/6	ENST00000329597.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA5	ENST00000329597.12	c.*38G>A		3_prime_UTR_variant	6/6	1	NM_000624.6	P1
SERPINA5	ENST00000554276.1	c.*38G>A		3_prime_UTR_variant	5/5	1		P1
SERPINA5	ENST00000553780.5	c.*38G>A		3_prime_UTR_variant	7/7	5		P1
SERPINA5	ENST00000554866.5	c.*38G>A		3_prime_UTR_variant	5/5	5		P1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3376 AN: 152192 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0267 AC: 6108 AN: 229152 Hom.: 100 AF XY: 0.0280 AC XY: 3444 AN XY: 123072

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.0522

Gnomad EAS exome AF: 0.0356

Gnomad SAS exome AF: 0.0408

Gnomad FIN exome AF: 0.0327

Gnomad NFE exome AF: 0.0228

Gnomad OTH exome AF: 0.0260

GnomAD4 exome AF: 0.0244 AC: 34996 AN: 1432776 Hom.: 511 Cov.: 31 AF XY: 0.0253 AC XY: 17939 AN XY: 709946

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.0192

Gnomad4 ASJ exome AF: 0.0477

Gnomad4 EAS exome AF: 0.0245

Gnomad4 SAS exome AF: 0.0406

Gnomad4 FIN exome AF: 0.0299

Gnomad4 NFE exome AF: 0.0228

Gnomad4 OTH exome AF: 0.0268

GnomAD4 genome AF: 0.0222 AC: 3378 AN: 152310 Hom.: 38 Cov.: 33 AF XY: 0.0229 AC XY: 1706 AN XY: 74482

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.0316

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0246 Hom.: 11

Bravo AF: 0.0216

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.6
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2069990; hg19: chr14-95058614; COSMIC: COSV61574220; COSMIC: COSV61574220;