rs13428251

Variant names:

• chr2-69787429-G-C
• rs13428251
• NM_001153.5:c.10-625G>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.10-625G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,104 control chromosomes in the GnomAD database, including 4,897 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 0.25 (4897 hom., cov: 33)
• Consequence: ANXA4 NM_001153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 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.10-625G>C		intron	N/A	NP_001144.1
	ANXA4	NM_001320698.2		c.10-625G>C		intron	N/A	NP_001307627.1
	ANXA4	NM_001365496.2		c.10-625G>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.10-625G>C		intron	N/A	ENSP00000377833.4
	ANXA4	ENST00000409920.5	TSL:1	c.10-625G>C		intron	N/A	ENSP00000386756.1
	ANXA4	ENST00000477632.5	TSL:1	n.137-625G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38410 AN: 151986 Hom.: 4889 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.253 AC: 38441 AN: 152104 Hom.: 4897 Cov.: 33 AF XY: 0.256 AC XY: 19025 AN XY: 74344

African (AFR) AF: 0.273 AC: 11329 AN: 41484

American (AMR) AF: 0.254 AC: 3880 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1718 AN: 5178

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4818

European-Finnish (FIN) AF: 0.271 AC: 2861 AN: 10556

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15553 AN: 67988

Other (OTH) AF: 0.250 AC: 528 AN: 2114

Alfa AF: 0.237 Hom.: 526

Bravo AF: 0.253

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.64
PhyloP100		-0.38
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: rs13428251; hg19: chr2-70014561;