4-121690130-G-A

Position:

• chr4-121690130-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001154.4(ANXA5):​c.10-3758C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,122 control chromosomes in the GnomAD database, including 4,168 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 0.23 (4168 hom., cov: 32)
• Consequence: ANXA5 NM_001154.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA5	NM_001154.4	c.10-3758C>T		intron_variant		ENST00000296511.10
ANXA5	XM_017008141.3	c.10-3758C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA5	ENST00000296511.10	c.10-3758C>T		intron_variant		1	NM_001154.4	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34280 AN: 152004 Hom.: 4162 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.226 AC: 34315 AN: 152122 Hom.: 4168 Cov.: 32 AF XY: 0.221 AC XY: 16419 AN XY: 74360

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.215

Alfa AF: 0.199 Hom.: 6291

Bravo AF: 0.235

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6857766; hg19: chr4-122611285;