rs4853017

Variant names:

• chr2-69784184-T-C
• rs4853017
• NM_001153.5:c.9+2610T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001153.5(ANXA4):​c.9+2610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,078 control chromosomes in the GnomAD database, including 10,877 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 0.36 (10877 hom., cov: 32)
• Consequence: ANXA4 NM_001153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001153.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA4	NM_001153.5	MANE Select	c.9+2610T>C		intron	N/A	NP_001144.1
	ANXA4	NM_001320698.2		c.9+2610T>C		intron	N/A	NP_001307627.1
	ANXA4	NM_001365496.2		c.9+2610T>C		intron	N/A	NP_001352425.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA4	ENST00000394295.6	TSL:1 MANE Select	c.9+2610T>C		intron	N/A	ENSP00000377833.4
	ANXA4	ENST00000409920.5	TSL:1	c.9+2610T>C		intron	N/A	ENSP00000386756.1
	ANXA4	ENST00000477632.5	TSL:1	n.136+2610T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54048 AN: 151960 Hom.: 10828 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.356 AC: 54155 AN: 152078 Hom.: 10877 Cov.: 32 AF XY: 0.362 AC XY: 26907 AN XY: 74326

African (AFR) AF: 0.498 AC: 20648 AN: 41462

American (AMR) AF: 0.480 AC: 7339 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1063 AN: 3468

East Asian (EAS) AF: 0.513 AC: 2654 AN: 5178

South Asian (SAS) AF: 0.371 AC: 1785 AN: 4816

European-Finnish (FIN) AF: 0.296 AC: 3136 AN: 10578

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16621 AN: 67984

Other (OTH) AF: 0.349 AC: 737 AN: 2112

Alfa AF: 0.334 Hom.: 1388

Bravo AF: 0.380

Asia WGS AF: 0.438 AC: 1524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.77
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4853017; hg19: chr2-70011316;