rs1079242

Variant names:

• chr10-80157952-A-G
• rs1079242
• NM_145868.2:c.1335+15T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145868.2(ANXA11):​c.1335+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,612,348 control chromosomes in the GnomAD database, including 206,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15398 hom., cov: 31)
  • Exomes 𝑓: 0.51 (191164 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.512
• Publications: 23 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-80157952-A-G is Benign according to our data. Variant chr10-80157952-A-G is described in ClinVar as Benign. ClinVar VariationId is 1244057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	NM_145868.2	MANE Select	c.1335+15T>C		intron	N/A	NP_665875.1
	ANXA11	NM_001157.3		c.1335+15T>C		intron	N/A	NP_001148.1
	ANXA11	NM_001278407.2		c.1335+15T>C		intron	N/A	NP_001265336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.1335+15T>C		intron	N/A	ENSP00000404412.2
	ANXA11	ENST00000372231.7	TSL:1	c.1335+15T>C		intron	N/A	ENSP00000361305.3
	ANXA11	ENST00000438331.5	TSL:1	c.1335+15T>C		intron	N/A	ENSP00000398610.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65331 AN: 151860 Hom.: 15396 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.449

GnomAD2 exomes AF: 0.482 AC: 121237 AN: 251306 AF XY: 0.481

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.518

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.574

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.507 AC: 740229 AN: 1460370 Hom.: 191164 Cov.: 35 AF XY: 0.503 AC XY: 365487 AN XY: 726640

African (AFR) AF: 0.209 AC: 7009 AN: 33464

American (AMR) AF: 0.514 AC: 22976 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 11277 AN: 26126

East Asian (EAS) AF: 0.589 AC: 23386 AN: 39694

South Asian (SAS) AF: 0.372 AC: 32062 AN: 86234

European-Finnish (FIN) AF: 0.562 AC: 30010 AN: 53406

Middle Eastern (MID) AF: 0.408 AC: 2348 AN: 5758

European-Non Finnish (NFE) AF: 0.524 AC: 582008 AN: 1110636

Other (OTH) AF: 0.483 AC: 29153 AN: 60338

GnomAD4 genome AF: 0.430 AC: 65339 AN: 151978 Hom.: 15398 Cov.: 31 AF XY: 0.432 AC XY: 32052 AN XY: 74268

African (AFR) AF: 0.217 AC: 9006 AN: 41462

American (AMR) AF: 0.474 AC: 7248 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3470

East Asian (EAS) AF: 0.583 AC: 2997 AN: 5138

South Asian (SAS) AF: 0.373 AC: 1795 AN: 4816

European-Finnish (FIN) AF: 0.576 AC: 6077 AN: 10558

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.519 AC: 35256 AN: 67948

Other (OTH) AF: 0.445 AC: 940 AN: 2110

Alfa AF: 0.495 Hom.: 31529

Bravo AF: 0.417

Asia WGS AF: 0.434 AC: 1506 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Inclusion body myopathy and brain white matter abnormalities (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.55
PhyloP100		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1079242; hg19: chr10-81917708; COSMIC: COSV55416414;