1-150979001-T-C

Variant names:

• chr1-150979001-T-C
• rs267734
• XM_047431989.1:c.-937T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 76 publications found

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]

ENSG00000231073 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANXA9	XM_047431989.1	c.-937T>C		5_prime_UTR_variant	Exon 1 of 15		XP_047287945.1
ANXA9	XM_047431991.1	c.-1098T>C		5_prime_UTR_variant	Exon 1 of 16		XP_047287947.1
ANXA9	XM_047431997.1	c.-1033T>C		5_prime_UTR_variant	Exon 1 of 16		XP_047287953.1
ANXA9	XM_047431999.1	c.-937T>C		5_prime_UTR_variant	Exon 1 of 14		XP_047287955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000231073	ENST00000808152.1	n.132-548T>C		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.0399 AC: 1649 AN: 41360

American (AMR) AF: 0.124 AC: 1882 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3466

East Asian (EAS) AF: 0.0258 AC: 133 AN: 5150

South Asian (SAS) AF: 0.0707 AC: 338 AN: 4780

European-Finnish (FIN) AF: 0.205 AC: 2157 AN: 10536

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14146 AN: 67906

Other (OTH) AF: 0.150 AC: 315 AN: 2098

Alfa AF: 0.182 Hom.: 9312

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
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs267734; hg19: chr1-150951477;