10-80189607-C-T

Variant names:

• chr10-80189607-C-T
• rs2573356
• NM_145868.2:c.-57-13452G>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.-57-13452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,050 control chromosomes in the GnomAD database, including 31,495 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 0.63 (31495 hom., cov: 32)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• 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: Genomics England PanelApp, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• inclusion body myopathy and brain white matter abnormalities

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	NM_145868.2	MANE Select	c.-57-13452G>A		intron	N/A	NP_665875.1
	ANXA11	NM_001157.3		c.-9+15736G>A		intron	N/A	NP_001148.1
	ANXA11	NM_001278407.2		c.-57-13452G>A		intron	N/A	NP_001265336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.-57-13452G>A		intron	N/A	ENSP00000404412.2
	ANXA11	ENST00000372231.7	TSL:1	c.-9+15736G>A		intron	N/A	ENSP00000361305.3
	ANXA11	ENST00000438331.5	TSL:1	c.-253-8471G>A		intron	N/A	ENSP00000398610.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96069 AN: 151932 Hom.: 31420 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.633 AC: 96202 AN: 152050 Hom.: 31495 Cov.: 32 AF XY: 0.629 AC XY: 46765 AN XY: 74334

African (AFR) AF: 0.802 AC: 33255 AN: 41462

American (AMR) AF: 0.580 AC: 8863 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2157 AN: 3466

East Asian (EAS) AF: 0.338 AC: 1751 AN: 5184

South Asian (SAS) AF: 0.641 AC: 3085 AN: 4812

European-Finnish (FIN) AF: 0.544 AC: 5747 AN: 10556

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39375 AN: 67966

Other (OTH) AF: 0.618 AC: 1303 AN: 2110

Alfa AF: 0.604 Hom.: 14490

Bravo AF: 0.641

Asia WGS AF: 0.559 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.3
DANN	Benign	0.71
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2573356; hg19: chr10-81949363;