chr10-80193200-G-A

Variant names:

• chr10-80193200-G-A
• rs2819945
• NM_145868.2:c.-58+12143C>T

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+12143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,986 control chromosomes in the GnomAD database, including 18,914 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 0.49 (18914 hom., cov: 32)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 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.-58+12143C>T		intron	N/A	NP_665875.1
	ANXA11	NM_001157.3		c.-9+12143C>T		intron	N/A	NP_001148.1
	ANXA11	NM_001278407.2		c.-58+12143C>T		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.-58+12143C>T		intron	N/A	ENSP00000404412.2
	ANXA11	ENST00000372231.7	TSL:1	c.-9+12143C>T		intron	N/A	ENSP00000361305.3
	ANXA11	ENST00000438331.5	TSL:1	c.-253-12064C>T		intron	N/A	ENSP00000398610.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73910 AN: 151868 Hom.: 18875 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.487 AC: 74000 AN: 151986 Hom.: 18914 Cov.: 32 AF XY: 0.482 AC XY: 35823 AN XY: 74268

African (AFR) AF: 0.637 AC: 26417 AN: 41472

American (AMR) AF: 0.367 AC: 5601 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1657 AN: 5166

South Asian (SAS) AF: 0.401 AC: 1930 AN: 4816

European-Finnish (FIN) AF: 0.455 AC: 4781 AN: 10510

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30308 AN: 67968

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.459 Hom.: 46300

Bravo AF: 0.485

Asia WGS AF: 0.406 AC: 1416 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	3.9
DANN	Benign	0.76
PhyloP100		-0.14
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: rs2819945; hg19: chr10-81952956;