2-69777196-C-A

Variant names:

• chr2-69777196-C-A
• rs2168116
• NM_001153.5:c.-46-4324C>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.-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
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt
ANXA4	NM_001153.5	c.-46-4324C>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.-46-4324C>A		intron_variant	Intron 1 of 12	1	NM_001153.5	ENSP00000377833.4

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

African (AFR) AF: 0.507 AC: 21004 AN: 41432

American (AMR) AF: 0.484 AC: 7385 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2643 AN: 5158

South Asian (SAS) AF: 0.371 AC: 1781 AN: 4802

European-Finnish (FIN) AF: 0.297 AC: 3133 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16555 AN: 67930

Other (OTH) AF: 0.348 AC: 734 AN: 2110

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
PhyloP100		-0.30
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: rs2168116; hg19: chr2-70004328;