Variant 2-69818669-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

ANXA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.351 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA4	NM_001153.5 linkuse as main transcript	c.699C>T	p.Ser233=	synonymous_variant	10/13	ENST00000394295.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA4	ENST00000394295.6 linkuse as main transcript	c.699C>T	p.Ser233=	synonymous_variant	10/13	1	NM_001153.5	P1	P09525-3

Frequencies

GnomAD3 genomes

AF:

0.00278

AC:

423

AN:

152086

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00278

AC:

423

AN:

152204

Hom.:

Cov.:

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.:

Bravo

AF:

0.00284

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over