chr10-80160044-T-C

Variant names:

• chr10-80160044-T-C
• rs2784773
• NM_145868.2:c.1181-849A>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.1181-849A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,056 control chromosomes in the GnomAD database, including 31,278 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 (31278 hom., cov: 32)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 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.1181-849A>G		intron	N/A	NP_665875.1	P50995-1
	ANXA11	NM_001157.3		c.1181-849A>G		intron	N/A	NP_001148.1	P50995-1
	ANXA11	NM_001278407.2		c.1181-849A>G		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.1181-849A>G		intron	N/A	ENSP00000404412.2	P50995-1
	ANXA11	ENST00000372231.7	TSL:1	c.1181-849A>G		intron	N/A	ENSP00000361305.3	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.1181-849A>G		intron	N/A	ENSP00000398610.1	P50995-1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96365 AN: 151938 Hom.: 31260 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.634 AC: 96417 AN: 152056 Hom.: 31278 Cov.: 32 AF XY: 0.643 AC XY: 47775 AN XY: 74338

African (AFR) AF: 0.526 AC: 21801 AN: 41474

American (AMR) AF: 0.713 AC: 10890 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2009 AN: 3468

East Asian (EAS) AF: 0.907 AC: 4679 AN: 5156

South Asian (SAS) AF: 0.854 AC: 4118 AN: 4824

European-Finnish (FIN) AF: 0.694 AC: 7351 AN: 10590

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43554 AN: 67960

Other (OTH) AF: 0.650 AC: 1370 AN: 2108

Alfa AF: 0.614 Hom.: 7229

Bravo AF: 0.630

Asia WGS AF: 0.840 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.75
DANN	Benign	0.14
PhyloP100		-1.1
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: rs2784773; hg19: chr10-81919800;