chr4-121679509-G-A

Position:

• chr4-121679509-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.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

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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA5	NM_001154.4	c.395-1015C>T		intron_variant		ENST00000296511.10	NP_001145.1
ANXA5	XM_017008141.3	c.*1247C>T		3_prime_UTR_variant	7/7		XP_016863630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA5	ENST00000296511.10	c.395-1015C>T		intron_variant		1	NM_001154.4	ENSP00000296511	P1

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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.431

Alfa AF: 0.455 Hom.: 7517

Bravo AF: 0.377

Asia WGS AF: 0.605 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.7
DANN	Benign	0.87

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: rs4833229; hg19: chr4-122600664;