rs7091565

Variant names:

• chr10-80153805-C-T
• rs7091565
• NM_145868.2:c.*2048G>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.*2048G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,126 control chromosomes in the GnomAD database, including 17,431 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 0.48 (17430 hom., cov: 33)
  • Exomes 𝑓: 0.39 (1 hom.)
• Consequence: ANXA11 NM_145868.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.*2048G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.*2048G>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_145868.2	ENSP00000404412.2
ANXA11	ENST00000372231.7	c.*2048G>A		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000361305.3
ANXA11	ENST00000438331.5	c.*2048G>A		3_prime_UTR_variant	Exon 17 of 17	1		ENSP00000398610.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72312 AN: 151980 Hom.: 17385 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.393 AC: 11 AN: 28 Hom.: 1 Cov.: 0 AF XY: 0.313 AC XY: 5 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.318 AC: 7 AN: 22

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.476 AC: 72415 AN: 152098 Hom.: 17430 Cov.: 33 AF XY: 0.476 AC XY: 35390 AN XY: 74352

African (AFR) AF: 0.540 AC: 22377 AN: 41472

American (AMR) AF: 0.447 AC: 6834 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2163 AN: 5166

South Asian (SAS) AF: 0.598 AC: 2882 AN: 4822

European-Finnish (FIN) AF: 0.445 AC: 4706 AN: 10586

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30530 AN: 67984

Other (OTH) AF: 0.471 AC: 995 AN: 2114

Alfa AF: 0.456 Hom.: 61102

Bravo AF: 0.481

Asia WGS AF: 0.537 AC: 1868 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	1.5
DANN	Benign	0.46
PhyloP100		-0.058
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: rs7091565; hg19: chr10-81913561; COSMIC: COSV55417897; COSMIC: COSV55417897;