rs12779955

Variant names:

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

Variant summary

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

The NM_145869.2(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 NM_145869.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 6 publications found

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]

ANXA11 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 23

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Ambry Genetics
• inclusion body myopathy and brain white matter abnormalities

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145869.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	NM_145868.2	MANE Select	c.-57-4953A>G		intron	N/A	NP_665875.1	P50995-1
	ANXA11	NM_001278408.2		c.-225A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	NP_001265337.1	P50995-1
	ANXA11	NM_145869.2		c.-225A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	NP_665876.1	P50995-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	ENST00000438331.5	TSL:1	c.-225A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	ENSP00000398610.1	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.-225A>G		5_prime_UTR	Exon 2 of 17	ENSP00000398610.1	P50995-1
	ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.-57-4953A>G		intron	N/A	ENSP00000404412.2	P50995-1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0506 AC: 2105 AN: 41576

American (AMR) AF: 0.202 AC: 3088 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3472

East Asian (EAS) AF: 0.0173 AC: 90 AN: 5190

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4820

European-Finnish (FIN) AF: 0.0918 AC: 973 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9081 AN: 68022

Other (OTH) AF: 0.133 AC: 282 AN: 2114

Alfa AF: 0.133 Hom.: 961

Bravo AF: 0.118

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.52
PhyloP100		0.017
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12779955; hg19: chr10-81940864;