4-78592061-A-G

Variant summary

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

The NM_005139.3(ANXA3):c.483+438A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,982 control chromosomes in the GnomAD database, including 26,869 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 0.59 (26869 hom., cov: 32)
• Consequence: ANXA3 NM_005139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

Genes affected

ANXA3 (HGNC:541): (annexin A3) This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. This protein functions in the inhibition of phopholipase A2 and cleavage of inositol 1,2-cyclic phosphate to form inositol 1-phosphate. This protein may also play a role in anti-coagulation. [provided by RefSeq, Jul 2008]

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 (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA3	NM_005139.3	c.483+438A>G		intron_variant		ENST00000264908.11
ANXA3	XM_047450154.1	c.483+438A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA3	ENST00000264908.11	c.483+438A>G		intron_variant		1	NM_005139.3	P1
ANXA3	ENST00000503570.6	c.366+438A>G		intron_variant		5
ANXA3	ENST00000512542.5	c.16-3320A>G		intron_variant		3
ANXA3	ENST00000512884.5	c.366+438A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89730 AN: 151866 Hom.: 26864 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.591 AC: 89787 AN: 151982 Hom.: 26869 Cov.: 32 AF XY: 0.587 AC XY: 43621 AN XY: 74268

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.619

Alfa AF: 0.631 Hom.: 63951

Bravo AF: 0.584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.5
Dann	Benign	0.44

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: rs2867461; hg19: chr4-79513215;