2-69821402-C-T

Variant summary

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

The NM_001153.5(ANXA4):​c.906+581C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,960 control chromosomes in the GnomAD database, including 4,330 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 0.23 ( 4330 hom., cov: 31)

Consequence

ANXA4
NM_001153.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANXA4NM_001153.5 linkc.906+581C>T intron_variant ENST00000394295.6 NP_001144.1 P09525-3Q6P452

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANXA4ENST00000394295.6 linkc.906+581C>T intron_variant 1 NM_001153.5 ENSP00000377833.4 P09525-3
ANXA4ENST00000409920.5 linkc.840+581C>T intron_variant 1 ENSP00000386756.1 Q6P452
ANXA4ENST00000471395.1 linkn.4090+581C>T intron_variant 1
ANXA4ENST00000477632.5 linkn.3630+581C>T intron_variant 1

Frequencies

GnomAD3 genomes
AF:
0.230
AC:
34869
AN:
151842
Hom.:
4328
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.147
Gnomad AMI
AF:
0.108
Gnomad AMR
AF:
0.241
Gnomad ASJ
AF:
0.353
Gnomad EAS
AF:
0.397
Gnomad SAS
AF:
0.324
Gnomad FIN
AF:
0.255
Gnomad MID
AF:
0.241
Gnomad NFE
AF:
0.249
Gnomad OTH
AF:
0.248
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.229
AC:
34873
AN:
151960
Hom.:
4330
Cov.:
31
AF XY:
0.233
AC XY:
17323
AN XY:
74260
show subpopulations
Gnomad4 AFR
AF:
0.147
Gnomad4 AMR
AF:
0.241
Gnomad4 ASJ
AF:
0.353
Gnomad4 EAS
AF:
0.396
Gnomad4 SAS
AF:
0.325
Gnomad4 FIN
AF:
0.255
Gnomad4 NFE
AF:
0.249
Gnomad4 OTH
AF:
0.247
Alfa
AF:
0.199
Hom.:
939
Bravo
AF:
0.224
Asia WGS
AF:
0.335
AC:
1164
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
7.6
DANN
Benign
0.66

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.

Other links and lift over

dbSNP: rs3816491; hg19: chr2-70048534; API