rs17718

Variant names:

• chr4-121668128-G-A
• rs17718
• NM_001154.4:c.*340C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ANXA5 Gene-Disease associations (from GenCC):

• pregnancy loss, recurrent, susceptibility to, 3

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001154.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA5	NM_001154.4	MANE Select	c.*340C>T		3_prime_UTR	Exon 13 of 13	NP_001145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA5	ENST00000296511.10	TSL:1 MANE Select	c.*340C>T		3_prime_UTR	Exon 13 of 13	ENSP00000296511.5
	ANXA5	ENST00000506395.5	TSL:5	n.*874C>T		non_coding_transcript_exon	Exon 13 of 13	ENSP00000421421.1
	ANXA5	ENST00000501272.6	TSL:5	c.*340C>T		3_prime_UTR	Exon 11 of 11	ENSP00000424106.1

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

African (AFR) AF: 0.182 AC: 176 AN: 966

American (AMR) AF: 0.0283 AC: 34 AN: 1200

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 64 AN: 1100

East Asian (EAS) AF: 0.00 AC: 0 AN: 1764

South Asian (SAS) AF: 0.00 AC: 0 AN: 566

European-Finnish (FIN) AF: 0.00431 AC: 4 AN: 928

Middle Eastern (MID) AF: 0.0726 AC: 9 AN: 124

European-Non Finnish (NFE) AF: 0.0181 AC: 309 AN: 17058

Other (OTH) AF: 0.0283 AC: 51 AN: 1804

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

African (AFR) AF: 0.193 AC: 8010 AN: 41454

American (AMR) AF: 0.0313 AC: 478 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4820

European-Finnish (FIN) AF: 0.00566 AC: 60 AN: 10594

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0186 AC: 1268 AN: 67996

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

Alfa AF: 0.0343 Hom.: 1086

Bravo AF: 0.0751

Asia WGS AF: 0.0180 AC: 62 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.57
DANN	Benign	0.43
PhyloP100		-0.54
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: rs17718; hg19: chr4-122589283;