rs2068927

Positions:

• chr2-69751813-G-A
• chr2-69751813-G-T

Variant summary

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

The NM_001153.5(ANXA4):​c.-47+9638G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,048 control chromosomes in the GnomAD database, including 6,746 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 0.30 (6746 hom., cov: 31)
• Consequence: ANXA4 NM_001153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

Genes affected

ANXA4 (HGNC:542): (annexin A4) Annexin IV (ANX4) belongs to the annexin family of calcium-dependent phospholipid binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. ANX4 has 45 to 59% identity with other members of its family and shares a similar size and exon-intron organization. Isolated from human placenta, ANX4 encodes a protein that has possible interactions with ATP, and has in vitro anticoagulant activity and also inhibits phospholipase A2 activity. ANX4 is almost exclusively expressed in epithelial cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2016]

ANXA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA4	NM_001153.5	c.-47+9638G>A		intron_variant		ENST00000394295.6	NP_001144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA4	ENST00000394295.6	c.-47+9638G>A		intron_variant		1	NM_001153.5	ENSP00000377833.4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45352 AN: 151930 Hom.: 6741 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.299 AC: 45390 AN: 152048 Hom.: 6746 Cov.: 31 AF XY: 0.296 AC XY: 22025 AN XY: 74312

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.304

Alfa AF: 0.186 Hom.: 401

Bravo AF: 0.300

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.69

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: rs2068927; hg19: chr2-69978945;