4-121693600-C-T

Variant names:

• chr4-121693600-C-T
• rs6830321
• NM_001154.4:c.9+2981G>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.9+2981G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,036 control chromosomes in the GnomAD database, including 16,111 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 0.44 (16111 hom., cov: 32)
• Consequence: ANXA5 NM_001154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 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.9+2981G>A		intron	N/A	NP_001145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA5	ENST00000296511.10	TSL:1 MANE Select	c.9+2981G>A		intron	N/A	ENSP00000296511.5
	ANXA5	ENST00000501272.6	TSL:5	c.9+2981G>A		intron	N/A	ENSP00000424106.1
	ANXA5	ENST00000515017.5	TSL:5	c.9+2981G>A		intron	N/A	ENSP00000424199.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66523 AN: 151916 Hom.: 16101 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.438 AC: 66552 AN: 152036 Hom.: 16111 Cov.: 32 AF XY: 0.448 AC XY: 33288 AN XY: 74316

African (AFR) AF: 0.229 AC: 9511 AN: 41478

American (AMR) AF: 0.512 AC: 7813 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1918 AN: 3472

East Asian (EAS) AF: 0.734 AC: 3778 AN: 5150

South Asian (SAS) AF: 0.598 AC: 2882 AN: 4820

European-Finnish (FIN) AF: 0.578 AC: 6109 AN: 10568

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33062 AN: 67968

Other (OTH) AF: 0.472 AC: 994 AN: 2108

Alfa AF: 0.475 Hom.: 57108

Bravo AF: 0.423

Asia WGS AF: 0.625 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.47
PhyloP100		0.0070
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: rs6830321; hg19: chr4-122614755;