rs2819941

Variant names:

• chr10-80201265-C-T
• rs2819941
• NM_145868.2:c.-58+4078G>A

Variant summary

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

The NM_145868.2(ANXA11):​c.-58+4078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,920 control chromosomes in the GnomAD database, including 33,041 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 0.65 (33041 hom., cov: 30)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145868.2. 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.-58+4078G>A		intron	N/A	NP_665875.1	P50995-1
	ANXA11	NM_001157.3		c.-9+4078G>A		intron	N/A	NP_001148.1	P50995-1
	ANXA11	NM_001278407.2		c.-58+4078G>A		intron	N/A	NP_001265336.1	Q5T0G8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.-58+4078G>A		intron	N/A	ENSP00000404412.2	P50995-1
	ANXA11	ENST00000372231.7	TSL:1	c.-9+4078G>A		intron	N/A	ENSP00000361305.3	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.-254+4078G>A		intron	N/A	ENSP00000398610.1	P50995-1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98580 AN: 151802 Hom.: 32968 Cov.: 30

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.650 AC: 98714 AN: 151920 Hom.: 33041 Cov.: 30 AF XY: 0.645 AC XY: 47843 AN XY: 74224

African (AFR) AF: 0.804 AC: 33330 AN: 41450

American (AMR) AF: 0.590 AC: 9006 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2374 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1672 AN: 5144

South Asian (SAS) AF: 0.674 AC: 3232 AN: 4798

European-Finnish (FIN) AF: 0.546 AC: 5760 AN: 10550

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.607 AC: 41245 AN: 67936

Other (OTH) AF: 0.635 AC: 1337 AN: 2104

Alfa AF: 0.614 Hom.: 76147

Bravo AF: 0.657

Asia WGS AF: 0.561 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.72
PhyloP100		0.038
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs2819941; hg19: chr10-81961021; COSMIC: COSV55415815;