4-121685788-C-T

Variant names:

• chr4-121685788-C-T
• rs12511956
• NM_001154.4:c.94+500G>A

Variant summary

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

The NM_001154.4(ANXA5):​c.94+500G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,106 control chromosomes in the GnomAD database, including 43,305 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 0.72 (43305 hom., cov: 31)
• Consequence: ANXA5 NM_001154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA5	NM_001154.4	c.94+500G>A		intron_variant	Intron 3 of 12	ENST00000296511.10	NP_001145.1
ANXA5	XM_017008141.3	c.94+500G>A		intron_variant	Intron 3 of 6		XP_016863630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA5	ENST00000296511.10	c.94+500G>A		intron_variant	Intron 3 of 12	1	NM_001154.4	ENSP00000296511.5

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109129 AN: 151988 Hom.: 43285 Cov.: 31

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.718 AC: 109169 AN: 152106 Hom.: 43305 Cov.: 31 AF XY: 0.727 AC XY: 54049 AN XY: 74370

African (AFR) AF: 0.349 AC: 14480 AN: 41438

American (AMR) AF: 0.826 AC: 12635 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2869 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5121 AN: 5156

South Asian (SAS) AF: 0.862 AC: 4156 AN: 4822

European-Finnish (FIN) AF: 0.929 AC: 9856 AN: 10610

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57523 AN: 68000

Other (OTH) AF: 0.757 AC: 1598 AN: 2112

Alfa AF: 0.798 Hom.: 23321

Bravo AF: 0.694

Asia WGS AF: 0.893 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.75
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12511956; hg19: chr4-122606943;