rs2168116

Positions:

• chr2-69777196-C-A
• chr2-69777196-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001153.5(ANXA4):​c.-46-4324C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,944 control chromosomes in the GnomAD database, including 11,063 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 0.36 (11063 hom., cov: 31)
• Consequence: ANXA4 NM_001153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA4	NM_001153.5	c.-46-4324C>A		intron_variant		ENST00000394295.6	NP_001144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA4	ENST00000394295.6	c.-46-4324C>A		intron_variant		1	NM_001153.5	ENSP00000377833	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54323 AN: 151824 Hom.: 11010 Cov.: 31

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.358 AC: 54435 AN: 151944 Hom.: 11063 Cov.: 31 AF XY: 0.364 AC XY: 27048 AN XY: 74266

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.348

Alfa AF: 0.307 Hom.: 1013

Bravo AF: 0.383

Asia WGS AF: 0.440 AC: 1528 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
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

Other links and lift over

dbSNP: rs2168116; hg19: chr2-70004328;