4-121693600-C-T

Position:

• chr4-121693600-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA5	NM_001154.4	c.9+2981G>A		intron_variant		ENST00000296511.10
ANXA5	XM_017008141.3	c.9+2981G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA5	ENST00000296511.10	c.9+2981G>A		intron_variant		1	NM_001154.4	P1

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

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.472

Alfa AF: 0.489 Hom.: 37012

Bravo AF: 0.423

Asia WGS AF: 0.625 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs6830321; hg19: chr4-122614755;