2-69751158-T-G

Variant names:

• chr2-69751158-T-G
• rs4852988
• NM_001153.5:c.-47+8983T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001153.5(ANXA4):​c.-47+8983T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,920 control chromosomes in the GnomAD database, including 29,523 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 0.60 (29523 hom., cov: 31)
• Consequence: ANXA4 NM_001153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA4	NM_001153.5	c.-47+8983T>G		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.-47+8983T>G		intron_variant	Intron 1 of 12	1	NM_001153.5	ENSP00000377833.4

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91582 AN: 151802 Hom.: 29466 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.604 AC: 91700 AN: 151920 Hom.: 29523 Cov.: 31 AF XY: 0.606 AC XY: 45002 AN XY: 74214

African (AFR) AF: 0.821 AC: 34013 AN: 41446

American (AMR) AF: 0.642 AC: 9783 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1215 AN: 3462

East Asian (EAS) AF: 0.717 AC: 3697 AN: 5158

South Asian (SAS) AF: 0.457 AC: 2197 AN: 4808

European-Finnish (FIN) AF: 0.586 AC: 6173 AN: 10536

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33036 AN: 67952

Other (OTH) AF: 0.549 AC: 1159 AN: 2110

Alfa AF: 0.514 Hom.: 3627

Bravo AF: 0.620

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.31
PhyloP100		-0.43
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

Publications

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Other links and lift over

dbSNP: rs4852988; hg19: chr2-69978290;