rs2573353

Variant names:

• chr10-80181161-C-A
• rs2573353
• NM_145868.2:c.-57-5006G>T

Variant summary

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

The NM_001278408.2(ANXA11):​c.-278G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,196 control chromosomes in the GnomAD database, including 31,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.63 (31448 hom., cov: 35)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: ANXA11 NM_001278408.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278408.2. 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.-57-5006G>T		intron	N/A	NP_665875.1
	ANXA11	NM_001278408.2		c.-278G>T		5_prime_UTR	Exon 2 of 17	NP_001265337.1
	ANXA11	NM_001157.3		c.-8-8292G>T		intron	N/A	NP_001148.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.-57-5006G>T		intron	N/A	ENSP00000404412.2
	ANXA11	ENST00000372231.7	TSL:1	c.-8-8292G>T		intron	N/A	ENSP00000361305.3
	ANXA11	ENST00000438331.5	TSL:1	c.-253-25G>T		intron	N/A	ENSP00000398610.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96056 AN: 152074 Hom.: 31380 Cov.: 35

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 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: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.632 AC: 96181 AN: 152192 Hom.: 31448 Cov.: 35 AF XY: 0.628 AC XY: 46746 AN XY: 74396

African (AFR) AF: 0.800 AC: 33220 AN: 41534

American (AMR) AF: 0.578 AC: 8846 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2159 AN: 3472

East Asian (EAS) AF: 0.337 AC: 1750 AN: 5186

South Asian (SAS) AF: 0.641 AC: 3095 AN: 4830

European-Finnish (FIN) AF: 0.545 AC: 5759 AN: 10562

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

European-Non Finnish (NFE) AF: 0.579 AC: 39372 AN: 67996

Other (OTH) AF: 0.615 AC: 1301 AN: 2114

Alfa AF: 0.627 Hom.: 5409

Bravo AF: 0.640

Asia WGS AF: 0.557 AC: 1939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.7
DANN	Benign	0.73
PhyloP100		0.054
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: rs2573353; hg19: chr10-81940917;