4-78592061-A-G

Variant names:

• chr4-78592061-A-G
• rs2867461
• NM_005139.3:c.483+438A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANXA3	NM_005139.3	c.483+438A>G		intron_variant	Intron 7 of 12	ENST00000264908.11	NP_005130.1
ANXA3	XM_047450154.1	c.483+438A>G		intron_variant	Intron 7 of 10		XP_047306110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA3	ENST00000264908.11	c.483+438A>G		intron_variant	Intron 7 of 12	1	NM_005139.3	ENSP00000264908.6
ANXA3	ENST00000503570.6	c.366+438A>G		intron_variant	Intron 8 of 13	5		ENSP00000421015.2
ANXA3	ENST00000512884.5	c.366+438A>G		intron_variant	Intron 6 of 11	5		ENSP00000423068.1
ANXA3	ENST00000512542.5	c.16-3320A>G		intron_variant	Intron 2 of 3	3		ENSP00000426591.1

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

African (AFR) AF: 0.505 AC: 20893 AN: 41408

American (AMR) AF: 0.563 AC: 8597 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2233 AN: 3472

East Asian (EAS) AF: 0.603 AC: 3117 AN: 5170

South Asian (SAS) AF: 0.547 AC: 2634 AN: 4814

European-Finnish (FIN) AF: 0.607 AC: 6420 AN: 10570

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43693 AN: 67958

Other (OTH) AF: 0.619 AC: 1308 AN: 2114

Alfa AF: 0.622 Hom.: 133789

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
PhyloP100		0.082
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: rs2867461; hg19: chr4-79513215;