rs3754210

Variant names:

• chr1-150981785-G-T
• rs3754210
• ENST00000808377.1:n.93-214C>A

Variant summary

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

The ENST00000808377.1(ENSG00000305070):​n.93-214C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,220 control chromosomes in the GnomAD database, including 3,519 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 0.18 (3519 hom., cov: 33)
• Consequence: ENSG00000305070 ENST00000808377.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 10 publications found

Genes affected

ENSG00000305070 (HGNC:):

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA9	XM_047431983.1	c.-192-516G>T		intron_variant	Intron 1 of 13		XP_047287939.1
ANXA9	XM_047431984.1	c.-193+118G>T		intron_variant	Intron 1 of 13		XP_047287940.1
ANXA9	XM_047431986.1	c.-193+118G>T		intron_variant	Intron 1 of 14		XP_047287942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000305070	ENST00000808377.1	n.93-214C>A		intron_variant	Intron 1 of 3
ENSG00000305070	ENST00000808378.1	n.92+322C>A		intron_variant	Intron 1 of 2
ENSG00000305070	ENST00000808379.1	n.87-237C>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26865 AN: 152102 Hom.: 3502 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.177 AC: 26926 AN: 152220 Hom.: 3519 Cov.: 33 AF XY: 0.175 AC XY: 13004 AN XY: 74424

African (AFR) AF: 0.370 AC: 15355 AN: 41498

American (AMR) AF: 0.118 AC: 1798 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 505 AN: 3472

East Asian (EAS) AF: 0.177 AC: 916 AN: 5174

South Asian (SAS) AF: 0.111 AC: 538 AN: 4826

European-Finnish (FIN) AF: 0.0937 AC: 994 AN: 10606

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0928 AC: 6312 AN: 68028

Other (OTH) AF: 0.160 AC: 338 AN: 2114

Alfa AF: 0.160 Hom.: 1814

Bravo AF: 0.189

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs3754210; hg19: chr1-150954261;