rs1050606

Variant names:

• chr4-121696891-A-C
• rs1050606
• NM_001154.4:c.-64T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-121696891-A-C
• chr4-121696891-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001154.4(ANXA5):​c.-64T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 294,552 control chromosomes in the GnomAD database, including 35,812 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 0.50 (19448 hom., cov: 33)
  • Exomes 𝑓: 0.47 (16364 hom.)
• Consequence: ANXA5 NM_001154.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA5	NM_001154.4	c.-64T>G		5_prime_UTR_variant	Exon 1 of 13	ENST00000296511.10	NP_001145.1
ANXA5	XM_017008141.3	c.-64T>G		5_prime_UTR_variant	Exon 1 of 7		XP_016863630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA5	ENST00000296511.10	c.-64T>G		5_prime_UTR_variant	Exon 1 of 13	1	NM_001154.4	ENSP00000296511.5

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76012 AN: 151944 Hom.: 19439 Cov.: 33

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.499

GnomAD4 exome AF: 0.474 AC: 67592 AN: 142492 Hom.: 16364 Cov.: 1 AF XY: 0.476 AC XY: 34324 AN XY: 72116

African (AFR) AF: 0.552 AC: 2475 AN: 4480

American (AMR) AF: 0.449 AC: 1807 AN: 4022

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 2592 AN: 5818

East Asian (EAS) AF: 0.209 AC: 2761 AN: 13214

South Asian (SAS) AF: 0.404 AC: 518 AN: 1282

European-Finnish (FIN) AF: 0.430 AC: 4495 AN: 10448

Middle Eastern (MID) AF: 0.455 AC: 362 AN: 796

European-Non Finnish (NFE) AF: 0.516 AC: 47777 AN: 92556

Other (OTH) AF: 0.487 AC: 4805 AN: 9876

GnomAD4 genome AF: 0.500 AC: 76056 AN: 152060 Hom.: 19448 Cov.: 33 AF XY: 0.491 AC XY: 36499 AN XY: 74350

African (AFR) AF: 0.560 AC: 23260 AN: 41500

American (AMR) AF: 0.462 AC: 7072 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1379 AN: 5130

South Asian (SAS) AF: 0.402 AC: 1937 AN: 4824

European-Finnish (FIN) AF: 0.413 AC: 4377 AN: 10596

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.511 AC: 34737 AN: 67936

Other (OTH) AF: 0.492 AC: 1040 AN: 2112

Alfa AF: 0.508 Hom.: 2405

Bravo AF: 0.508

Asia WGS AF: 0.357 AC: 1244 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.63
PhyloP100		-0.56
PromoterAI		-0.021	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1050606; hg19: chr4-122618046;