rs3851054

Variant names:

• chr10-80173550-A-G
• rs3851054
• NM_145868.2:c.-8-681T>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.-8-681T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,986 control chromosomes in the GnomAD database, including 25,387 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 0.57 (25387 hom., cov: 32)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.-8-681T>C		intron_variant	Intron 2 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.-8-681T>C		intron_variant	Intron 2 of 15	1	NM_145868.2	ENSP00000404412.2
ANXA11	ENST00000372231.7	c.-8-681T>C		intron_variant	Intron 1 of 14	1		ENSP00000361305.3
ANXA11	ENST00000438331.5	c.-8-681T>C		intron_variant	Intron 3 of 16	1		ENSP00000398610.1
ANXA11	ENST00000463657.1	n.745-681T>C		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86370 AN: 151868 Hom.: 25321 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.569 AC: 86497 AN: 151986 Hom.: 25387 Cov.: 32 AF XY: 0.567 AC XY: 42117 AN XY: 74338

African (AFR) AF: 0.718 AC: 29765 AN: 41442

American (AMR) AF: 0.533 AC: 8139 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1898 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1738 AN: 5156

South Asian (SAS) AF: 0.602 AC: 2904 AN: 4824

European-Finnish (FIN) AF: 0.484 AC: 5116 AN: 10572

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.517 AC: 35114 AN: 67934

Other (OTH) AF: 0.576 AC: 1216 AN: 2110

Alfa AF: 0.559 Hom.: 3117

Bravo AF: 0.581

Asia WGS AF: 0.535 AC: 1862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		-0.018
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: rs3851054; hg19: chr10-81933306;