2-69758303-G-A

Variant names:

• chr2-69758303-G-A
• rs7597155
• NM_001153.5:c.-47+16128G>A

Variant summary

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

The NM_001153.5(ANXA4):​c.-47+16128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,086 control chromosomes in the GnomAD database, including 19,447 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 0.50 (19447 hom., cov: 33)
• Consequence: ANXA4 NM_001153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• Publications: 14 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA4	NM_001153.5	c.-47+16128G>A		intron_variant	Intron 1 of 12	ENST00000394295.6	NP_001144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA4	ENST00000394295.6	c.-47+16128G>A		intron_variant	Intron 1 of 12	1	NM_001153.5	ENSP00000377833.4

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75735 AN: 151968 Hom.: 19421 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.498 AC: 75809 AN: 152086 Hom.: 19447 Cov.: 33 AF XY: 0.505 AC XY: 37557 AN XY: 74336

African (AFR) AF: 0.452 AC: 18780 AN: 41514

American (AMR) AF: 0.596 AC: 9107 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3470

East Asian (EAS) AF: 0.789 AC: 4065 AN: 5154

South Asian (SAS) AF: 0.451 AC: 2175 AN: 4820

European-Finnish (FIN) AF: 0.570 AC: 6022 AN: 10568

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.486 AC: 33006 AN: 67964

Other (OTH) AF: 0.473 AC: 997 AN: 2108

Alfa AF: 0.486 Hom.: 11930

Bravo AF: 0.501

Asia WGS AF: 0.585 AC: 2033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.93
DANN	Benign	0.71
PhyloP100		-0.52
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: rs7597155; hg19: chr2-69985435;