rs4970988

Positions:

• chr1-150977586-G-A
• chr1-150977586-G-T

Variant summary

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

The XM_047431989.1(ANXA9):​c.-2352G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,150 control chromosomes in the GnomAD database, including 8,435 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 0.31 (8435 hom., cov: 32)
• Consequence: ANXA9 XM_047431989.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.765

Genes affected

ANXA9 (HGNC:547): (annexin A9) The annexins are a family of calcium-dependent phospholipid-binding proteins. Members of the annexin family contain 4 internal repeat domains, each of which includes a type II calcium-binding site. The calcium-binding sites are required for annexins to aggregate and cooperatively bind anionic phospholipids and extracellular matrix proteins. This gene encodes a divergent member of the annexin protein family in which all four homologous type II calcium-binding sites in the conserved tetrad core contain amino acid substitutions that ablate their function. However, structural analysis suggests that the conserved putative ion channel formed by the tetrad core is intact. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA9	XM_047431989.1	c.-2352G>A		5_prime_UTR_variant	1/15		XP_047287945.1
ANXA9	XM_047431991.1	c.-2513G>A		upstream_gene_variant			XP_047287947.1
ANXA9	XM_047431997.1	c.-2448G>A		upstream_gene_variant			XP_047287953.1
ANXA9	XM_047431999.1	c.-2352G>A		upstream_gene_variant			XP_047287955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46752 AN: 152032 Hom.: 8430 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.307 AC: 46760 AN: 152150 Hom.: 8435 Cov.: 32 AF XY: 0.315 AC XY: 23454 AN XY: 74364

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.329

Alfa AF: 0.249 Hom.: 1070

Bravo AF: 0.307

Asia WGS AF: 0.412 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4970988; hg19: chr1-150950062;