10-80177467-T-C

Variant names:

• chr10-80177467-T-C
• rs10887581
• NM_145868.2:c.-57-1312A>G

Variant summary

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

The NM_001157.3(ANXA11):​c.-8-4598A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,954 control chromosomes in the GnomAD database, including 9,458 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 0.35 (9458 hom., cov: 31)
• Consequence: ANXA11 NM_001157.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001157.3. 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.-57-1312A>G		intron	N/A	NP_665875.1
	ANXA11	NM_001157.3		c.-8-4598A>G		intron	N/A	NP_001148.1
	ANXA11	NM_001278407.2		c.-57-1312A>G		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.-57-1312A>G		intron	N/A	ENSP00000404412.2
	ANXA11	ENST00000372231.7	TSL:1	c.-8-4598A>G		intron	N/A	ENSP00000361305.3
	ANXA11	ENST00000438331.5	TSL:1	c.-57-1312A>G		intron	N/A	ENSP00000398610.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52690 AN: 151836 Hom.: 9430 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.347 AC: 52765 AN: 151954 Hom.: 9458 Cov.: 31 AF XY: 0.345 AC XY: 25649 AN XY: 74268

African (AFR) AF: 0.403 AC: 16679 AN: 41396

American (AMR) AF: 0.244 AC: 3734 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1652 AN: 5158

South Asian (SAS) AF: 0.348 AC: 1678 AN: 4820

European-Finnish (FIN) AF: 0.370 AC: 3902 AN: 10540

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23016 AN: 67974

Other (OTH) AF: 0.334 AC: 705 AN: 2108

Alfa AF: 0.229 Hom.: 707

Bravo AF: 0.341

Asia WGS AF: 0.361 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.71
PhyloP100		-1.0
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: rs10887581; hg19: chr10-81937223;