ENST00000438331.5:c.-225A>G

Variant names:

• chr10-80181108-T-C
• rs12779955
• ENST00000438331.5:c.-225A>G

Variant summary

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

The ENST00000438331.5(ANXA11):​c.-225A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,294 control chromosomes in the GnomAD database, including 1,205 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 0.11 (1205 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: ANXA11 ENST00000438331.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

Genes affected

ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.-57-4953A>G		intron_variant	Intron 1 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.-57-4953A>G		intron_variant	Intron 1 of 15	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17249 AN: 152172 Hom.: 1199 Cov.: 33

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.113 AC: 17270 AN: 152290 Hom.: 1205 Cov.: 33 AF XY: 0.116 AC XY: 8635 AN XY: 74460

Gnomad4 AFR AF: 0.0506

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0173

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.133

Alfa AF: 0.138 Hom.: 699

Bravo AF: 0.118

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs12779955; hg19: chr10-81940864;