rs267734

Positions:

• chr1-150979001-T-C

Variant summary

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

The XM_047431989.1(ANXA9):​c.-937T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,706 control chromosomes in the GnomAD database, including 2,004 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 0.14 (2004 hom., cov: 30)
• Consequence: ANXA9 XM_047431989.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA9	XM_047431989.1	c.-937T>C		5_prime_UTR_variant	1/15		XP_047287945.1
ANXA9	XM_047431991.1	c.-1098T>C		5_prime_UTR_variant	1/16		XP_047287947.1
ANXA9	XM_047431997.1	c.-1033T>C		5_prime_UTR_variant	1/16		XP_047287953.1
ANXA9	XM_047431999.1	c.-937T>C		5_prime_UTR_variant	1/14		XP_047287955.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21600 AN: 151588 Hom.: 2004 Cov.: 30

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.142 AC: 21595 AN: 151706 Hom.: 2004 Cov.: 30 AF XY: 0.141 AC XY: 10462 AN XY: 74136

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.0707

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.150

Alfa AF: 0.189 Hom.: 3862

Bravo AF: 0.132

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs267734; hg19: chr1-150951477;