10-80155380-T-C

Variant names:

• chr10-80155380-T-C
• rs2789686
• NM_145868.2:c.*473A>G

Variant summary

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

The NM_145868.2(ANXA11):​c.*473A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 156,018 control chromosomes in the GnomAD database, including 56,354 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 0.84 (54766 hom., cov: 32)
  • Exomes 𝑓: 0.90 (1588 hom.)
• Consequence: ANXA11 NM_145868.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 16 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.*473A>G		3_prime_UTR	Exon 16 of 16	NP_665875.1	P50995-1
	ANXA11	NM_001157.3		c.*473A>G		3_prime_UTR	Exon 15 of 15	NP_001148.1	P50995-1
	ANXA11	NM_001278407.2		c.*473A>G		3_prime_UTR	Exon 17 of 17	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.*473A>G		3_prime_UTR	Exon 16 of 16	ENSP00000404412.2	P50995-1
	ANXA11	ENST00000372231.7	TSL:1	c.*473A>G		3_prime_UTR	Exon 15 of 15	ENSP00000361305.3	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.*473A>G		3_prime_UTR	Exon 17 of 17	ENSP00000398610.1	P50995-1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128384 AN: 152038 Hom.: 54714 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.864

GnomAD4 exome AF: 0.905 AC: 3495 AN: 3862 Hom.: 1588 Cov.: 0 AF XY: 0.909 AC XY: 1845 AN XY: 2030

African (AFR) AF: 0.750 AC: 39 AN: 52

American (AMR) AF: 0.933 AC: 586 AN: 628

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 59 AN: 76

East Asian (EAS) AF: 1.00 AC: 102 AN: 102

South Asian (SAS) AF: 0.960 AC: 215 AN: 224

European-Finnish (FIN) AF: 0.914 AC: 435 AN: 476

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.892 AC: 1929 AN: 2162

Other (OTH) AF: 0.920 AC: 127 AN: 138

GnomAD4 genome AF: 0.844 AC: 128488 AN: 152156 Hom.: 54766 Cov.: 32 AF XY: 0.848 AC XY: 63051 AN XY: 74394

African (AFR) AF: 0.715 AC: 29640 AN: 41480

American (AMR) AF: 0.873 AC: 13355 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2738 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5162 AN: 5168

South Asian (SAS) AF: 0.955 AC: 4606 AN: 4822

European-Finnish (FIN) AF: 0.917 AC: 9719 AN: 10600

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60428 AN: 68000

Other (OTH) AF: 0.866 AC: 1833 AN: 2116

Alfa AF: 0.875 Hom.: 96932

Bravo AF: 0.838

Asia WGS AF: 0.958 AC: 3332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.31
PhyloP100		-0.56
Mutation Taster		=100/0	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: rs2789686; hg19: chr10-81915136;