rs1396799

Positions:

• chr2-69660751-G-A

Variant summary

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

The NM_001320698.2(ANXA4):​c.-145+7469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 151,632 control chromosomes in the GnomAD database, including 1,117 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 0.071 (1117 hom., cov: 31)
• Consequence: ANXA4 NM_001320698.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA4	NM_001320698.2	c.-145+7469G>A		intron_variant			NP_001307627.1
ANXA4	XM_017003943.2	c.-302+7469G>A		intron_variant			XP_016859432.1
ANXA4	XM_024452835.2	c.-2827+7469G>A		intron_variant			XP_024308603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA4	ENST00000418066.2	n.766+7469G>A		intron_variant		3
AAK1	ENST00000461002.1	n.327+13272C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10685 AN: 151514 Hom.: 1115 Cov.: 31

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00746

Gnomad OTH AF: 0.0668

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

GnomAD4 genome AF: 0.0705 AC: 10697 AN: 151632 Hom.: 1117 Cov.: 31 AF XY: 0.0785 AC XY: 5814 AN XY: 74072

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.0361

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.0635

Gnomad4 NFE AF: 0.00746

Gnomad4 OTH AF: 0.0666

Alfa AF: 0.0377 Hom.: 60

Bravo AF: 0.0869

Asia WGS AF: 0.247 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1396799; hg19: chr2-69887883;