rs12763624

Variant names:

• chr10-80165074-C-T
• rs12763624
• NM_145868.2:c.859-931G>A

Variant summary

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

The NM_145868.2(ANXA11):​c.859-931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,202 control chromosomes in the GnomAD database, including 2,934 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 0.18 (2934 hom., cov: 33)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.859-931G>A		intron_variant	Intron 8 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.859-931G>A		intron_variant	Intron 8 of 15	1	NM_145868.2	ENSP00000404412.2
ANXA11	ENST00000372231.7	c.859-931G>A		intron_variant	Intron 7 of 14	1		ENSP00000361305.3
ANXA11	ENST00000438331.5	c.859-931G>A		intron_variant	Intron 9 of 16	1		ENSP00000398610.1
ANXA11	ENST00000265447.8	c.760-931G>A		intron_variant	Intron 7 of 14	5		ENSP00000265447.5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26919 AN: 152084 Hom.: 2937 Cov.: 33

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.177 AC: 26915 AN: 152202 Hom.: 2934 Cov.: 33 AF XY: 0.173 AC XY: 12855 AN XY: 74414

African (AFR) AF: 0.0678 AC: 2814 AN: 41532

American (AMR) AF: 0.153 AC: 2346 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3468

East Asian (EAS) AF: 0.104 AC: 540 AN: 5180

South Asian (SAS) AF: 0.107 AC: 518 AN: 4820

European-Finnish (FIN) AF: 0.228 AC: 2419 AN: 10596

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16856 AN: 67984

Other (OTH) AF: 0.185 AC: 389 AN: 2108

Alfa AF: 0.220 Hom.: 4975

Bravo AF: 0.169

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.49
PhyloP100		-0.29
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: rs12763624; hg19: chr10-81924830;