Variant 4-121696533-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001154.4(ANXA5):c.9+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,333,308 control chromosomes in the GnomAD database, including 15,025 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 0.18 ( 2512 hom., cov: 33)

Exomes 𝑓: 0.14 ( 12513 hom. )

Consequence

ANXA5
NM_001154.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.26

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA5	NM_001154.4 linkuse as main transcript	c.9+48A>G		intron_variant		ENST00000296511.10	NP_001145.1
ANXA5	XM_017008141.3 linkuse as main transcript	c.9+48A>G		intron_variant			XP_016863630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA5	ENST00000296511.10 linkuse as main transcript	c.9+48A>G		intron_variant		1	NM_001154.4	ENSP00000296511	P1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26750

AN:

152102

Hom.:

2505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.132

AC:

16417

AN:

124724

Hom.:

1123

AF XY:

0.129

AC XY:

8637

AN XY:

67184

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.0819

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.0985

Gnomad NFE exome

AF:

0.127

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.141

AC:

166357

AN:

1181088

Hom.:

12513

Cov.:

AF XY:

0.140

AC XY:

80104

AN XY:

571864

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.176

AC:

26785

AN:

152220

Hom.:

2512

Cov.:

AF XY:

0.174

AC XY:

12962

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.147

Hom.:

3583

Bravo

AF:

0.184

Asia WGS

AF:

0.194

AC:

673

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

1.1

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over