rs2069990

Variant names:

• chr14-94592277-G-A
• rs2069990
• NM_000624.6:c.*38G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

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]

ENSG00000273259 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA5	NM_000624.6	c.*38G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000329597.12	NP_000615.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA5	ENST00000329597.12	c.*38G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_000624.6	ENSP00000333203.7
ENSG00000273259	ENST00000553947.1	n.77+141G>A		intron_variant	Intron 1 of 7	2		ENSP00000452367.2

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

GnomAD2 exomes AF: 0.0267 AC: 6108 AN: 229152 AF XY: 0.0280

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 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

African (AFR) AF: 0.0138 AC: 451 AN: 32702

American (AMR) AF: 0.0192 AC: 812 AN: 42366

Ashkenazi Jewish (ASJ) AF: 0.0477 AC: 1165 AN: 24398

East Asian (EAS) AF: 0.0245 AC: 967 AN: 39398

South Asian (SAS) AF: 0.0406 AC: 3330 AN: 82120

European-Finnish (FIN) AF: 0.0299 AC: 1568 AN: 52472

Middle Eastern (MID) AF: 0.0239 AC: 134 AN: 5606

European-Non Finnish (NFE) AF: 0.0228 AC: 24986 AN: 1094574

Other (OTH) AF: 0.0268 AC: 1583 AN: 59140

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

African (AFR) AF: 0.0142 AC: 589 AN: 41560

American (AMR) AF: 0.0240 AC: 367 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3472

East Asian (EAS) AF: 0.0297 AC: 154 AN: 5180

South Asian (SAS) AF: 0.0321 AC: 155 AN: 4828

European-Finnish (FIN) AF: 0.0316 AC: 336 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0230 AC: 1568 AN: 68028

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0240 Hom.: 17

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
PhyloP100		0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2069990; hg19: chr14-95058614; COSMIC: COSV61574220; COSMIC: COSV61574220;