4-78585710-G-T

Variant names:

• chr4-78585710-G-T
• rs7679218
• NM_005139.3:c.313-550G>T

Variant summary

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

The NM_005139.3(ANXA3):​c.313-550G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,060 control chromosomes in the GnomAD database, including 40,334 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 0.72 (40334 hom., cov: 32)
• Consequence: ANXA3 NM_005139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA3	NM_005139.3	c.313-550G>T		intron_variant	Intron 5 of 12	ENST00000264908.11	NP_005130.1
ANXA3	XM_047450154.1	c.313-550G>T		intron_variant	Intron 5 of 10		XP_047306110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA3	ENST00000264908.11	c.313-550G>T		intron_variant	Intron 5 of 12	1	NM_005139.3	ENSP00000264908.6

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110119 AN: 151946 Hom.: 40302 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.725 AC: 110208 AN: 152060 Hom.: 40334 Cov.: 32 AF XY: 0.723 AC XY: 53721 AN XY: 74318

African (AFR) AF: 0.810 AC: 33604 AN: 41476

American (AMR) AF: 0.634 AC: 9692 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2403 AN: 3470

East Asian (EAS) AF: 0.874 AC: 4526 AN: 5178

South Asian (SAS) AF: 0.710 AC: 3415 AN: 4810

European-Finnish (FIN) AF: 0.685 AC: 7242 AN: 10576

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46852 AN: 67958

Other (OTH) AF: 0.728 AC: 1533 AN: 2106

Alfa AF: 0.700 Hom.: 50278

Bravo AF: 0.724

Asia WGS AF: 0.769 AC: 2672 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.49
PhyloP100		0.099
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: rs7679218; hg19: chr4-79506864;