rs17718

Positions:

• chr4-121668128-G-A

Variant summary

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

The NM_001154.4(ANXA5):​c.*340C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 177,608 control chromosomes in the GnomAD database, including 866 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 0.067 (840 hom., cov: 32)
  • Exomes 𝑓: 0.025 (26 hom.)
• Consequence: ANXA5 NM_001154.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544

Genes affected

ANXA5 (HGNC:543): (annexin A5) The Annexin 5 gene spans 29 kb containing 13 exons, and encodes a single transcript of approximately 1.6 kb and a protein product with a molecular weight of about 35 kDa.The protein encoded by this gene belongs to the annexin family of calcium-dependent phospholipid binding proteins some of which have been implicated in membrane-related events along exocytotic and endocytotic pathways. Annexin 5 is a phospholipase A2 and protein kinase C inhibitory protein with calcium channel activity and a potential role in cellular signal transduction, inflammation, growth and differentiation. Annexin 5 has also been described as placental anticoagulant protein I, vascular anticoagulant-alpha, endonexin II, lipocortin V, placental protein 4 and anchorin CII. Polymorphisms in this gene have been implicated in various obstetric complications. [provided by RefSeq, Dec 2019]

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 (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA5	NM_001154.4	c.*340C>T		3_prime_UTR_variant	13/13	ENST00000296511.10	NP_001145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA5	ENST00000296511	c.*340C>T		3_prime_UTR_variant	13/13	1	NM_001154.4	ENSP00000296511.5

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10189 AN: 151980 Hom.: 835 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00566

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0564

GnomAD4 exome AF: 0.0254 AC: 647 AN: 25510 Hom.: 26 Cov.: 0 AF XY: 0.0252 AC XY: 324 AN XY: 12842

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.0283

Gnomad4 ASJ exome AF: 0.0582

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00431

Gnomad4 NFE exome AF: 0.0181

Gnomad4 OTH exome AF: 0.0283

GnomAD4 genome AF: 0.0671 AC: 10209 AN: 152098 Hom.: 840 Cov.: 32 AF XY: 0.0645 AC XY: 4794 AN XY: 74352

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.00566

Gnomad4 NFE AF: 0.0186

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0271 Hom.: 257

Bravo AF: 0.0751

Asia WGS AF: 0.0180 AC: 62 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.57
DANN	Benign	0.43

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: rs17718; hg19: chr4-122589283;