rs4833229

Variant names:

• chr4-121679509-G-A
• rs4833229
• NM_001154.4:c.395-1015C>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.395-1015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,924 control chromosomes in the GnomAD database, including 14,132 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 0.40 (14132 hom., cov: 31)
• Consequence: ANXA5 NM_001154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA5	NM_001154.4	MANE Select	c.395-1015C>T		intron	N/A	NP_001145.1	P08758

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA5	ENST00000296511.10	TSL:1 MANE Select	c.395-1015C>T		intron	N/A	ENSP00000296511.5	P08758
	ANXA5	ENST00000969932.1		c.500-1015C>T		intron	N/A	ENSP00000639991.1
	ANXA5	ENST00000969927.1		c.395-1015C>T		intron	N/A	ENSP00000639986.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60032 AN: 151806 Hom.: 14121 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.424

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.395 AC: 60053 AN: 151924 Hom.: 14132 Cov.: 31 AF XY: 0.407 AC XY: 30186 AN XY: 74224

African (AFR) AF: 0.135 AC: 5601 AN: 41446

American (AMR) AF: 0.493 AC: 7518 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1883 AN: 3468

East Asian (EAS) AF: 0.691 AC: 3568 AN: 5164

South Asian (SAS) AF: 0.590 AC: 2834 AN: 4806

European-Finnish (FIN) AF: 0.566 AC: 5961 AN: 10534

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 31334 AN: 67950

Other (OTH) AF: 0.431 AC: 906 AN: 2104

Alfa AF: 0.452 Hom.: 8357

Bravo AF: 0.377

Asia WGS AF: 0.605 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.7
DANN	Benign	0.87
PhyloP100		-0.086
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: rs4833229; hg19: chr4-122600664;