NM_145868.2:c.-57-6342T>C

Variant names:

• chr10-80182497-A-G
• rs7913325
• NM_145868.2:c.-57-6342T>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.-57-6342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 152,264 control chromosomes in the GnomAD database, including 454 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 0.064 (454 hom., cov: 32)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61
• Publications: 2 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 = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.-57-6342T>C		intron_variant	Intron 1 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.-57-6342T>C		intron_variant	Intron 1 of 15	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9679 AN: 152146 Hom.: 453 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0781

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

GnomAD4 genome AF: 0.0636 AC: 9684 AN: 152264 Hom.: 454 Cov.: 32 AF XY: 0.0620 AC XY: 4615 AN XY: 74444

African (AFR) AF: 0.108 AC: 4491 AN: 41524

American (AMR) AF: 0.0719 AC: 1099 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4824

European-Finnish (FIN) AF: 0.0204 AC: 217 AN: 10618

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0445 AC: 3029 AN: 68026

Other (OTH) AF: 0.0773 AC: 163 AN: 2110

Alfa AF: 0.0563 Hom.: 40

Bravo AF: 0.0699

Asia WGS AF: 0.0160 AC: 59 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.67
PhyloP100		-2.6
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: rs7913325; hg19: chr10-81942253;