rs6585424

Variant names:

• chr10-80173992-A-G
• rs6585424
• NM_145868.2:c.-8-1123T>C

Variant summary

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

The NM_145868.2(ANXA11):​c.-8-1123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,232 control chromosomes in the GnomAD database, including 1,385 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 0.13 (1385 hom., cov: 33)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• Publications: 19 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 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.-8-1123T>C		intron	N/A	NP_665875.1	P50995-1
	ANXA11	NM_001157.3		c.-8-1123T>C		intron	N/A	NP_001148.1	P50995-1
	ANXA11	NM_001278407.2		c.-8-1123T>C		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.-8-1123T>C		intron	N/A	ENSP00000404412.2	P50995-1
	ANXA11	ENST00000372231.7	TSL:1	c.-8-1123T>C		intron	N/A	ENSP00000361305.3	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.-8-1123T>C		intron	N/A	ENSP00000398610.1	P50995-1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19530 AN: 152114 Hom.: 1379 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.128 AC: 19560 AN: 152232 Hom.: 1385 Cov.: 33 AF XY: 0.130 AC XY: 9678 AN XY: 74422

African (AFR) AF: 0.104 AC: 4301 AN: 41550

American (AMR) AF: 0.207 AC: 3164 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3468

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5176

South Asian (SAS) AF: 0.240 AC: 1155 AN: 4814

European-Finnish (FIN) AF: 0.0919 AC: 974 AN: 10598

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9079 AN: 68010

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.135 Hom.: 1403

Bravo AF: 0.136

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.68
PhyloP100		-0.81
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: rs6585424; hg19: chr10-81933748;