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GeneBe

2-69818669-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001153.5(ANXA4):c.699C>T(p.Ser233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,608,110 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0044 ( 11 hom. )

Consequence

ANXA4
NM_001153.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.351
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-69818669-C-T is Benign according to our data. Variant chr2-69818669-C-T is described in ClinVar as [Benign]. Clinvar id is 774594.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.351 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANXA4NM_001153.5 linkuse as main transcriptc.699C>T p.Ser233= synonymous_variant 10/13 ENST00000394295.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANXA4ENST00000394295.6 linkuse as main transcriptc.699C>T p.Ser233= synonymous_variant 10/131 NM_001153.5 P1P09525-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00278
AC:
423
AN:
152086
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000628
Gnomad AMI
AF:
0.0132
Gnomad AMR
AF:
0.000786
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.000661
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00516
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00256
AC:
635
AN:
248068
Hom.:
2
AF XY:
0.00247
AC XY:
332
AN XY:
134190
show subpopulations
Gnomad AFR exome
AF:
0.000685
Gnomad AMR exome
AF:
0.000480
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000635
Gnomad FIN exome
AF:
0.000833
Gnomad NFE exome
AF:
0.00480
Gnomad OTH exome
AF:
0.00268
GnomAD4 exome
AF:
0.00438
AC:
6370
AN:
1455906
Hom.:
11
Cov.:
28
AF XY:
0.00416
AC XY:
3012
AN XY:
724280
show subpopulations
Gnomad4 AFR exome
AF:
0.000842
Gnomad4 AMR exome
AF:
0.000567
Gnomad4 ASJ exome
AF:
0.00153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000644
Gnomad4 FIN exome
AF:
0.000956
Gnomad4 NFE exome
AF:
0.00539
Gnomad4 OTH exome
AF:
0.00313
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00278
AC:
423
AN:
152204
Hom.:
1
Cov.:
32
AF XY:
0.00234
AC XY:
174
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.000626
Gnomad4 AMR
AF:
0.000785
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.000661
Gnomad4 NFE
AF:
0.00516
Gnomad4 OTH
AF:
0.00332
Alfa
AF:
0.00416
Hom.:
0
Bravo
AF:
0.00284
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
7.4
Dann
Benign
0.65

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: rs116265883; hg19: chr2-70045801; API