10-80162162-T-C

Variant names:

• chr10-80162162-T-C
• rs2245168
• NM_145868.2:c.1087-134A>G

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.1087-134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 662,152 control chromosomes in the GnomAD database, including 59,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11394 hom., cov: 34)
  • Exomes 𝑓: 0.42 (47682 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.110
• Publications: 8 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=-0.92).
• BP6: Variant 10-80162162-T-C is Benign according to our data. Variant chr10-80162162-T-C is described in ClinVar as Benign. ClinVar VariationId is 1281123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.1087-134A>G		intron_variant	Intron 11 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.1087-134A>G		intron_variant	Intron 11 of 15	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56114 AN: 152048 Hom.: 11392 Cov.: 34

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.421 AC: 214761 AN: 509986 Hom.: 47682 AF XY: 0.419 AC XY: 111405 AN XY: 265788

African (AFR) AF: 0.201 AC: 2951 AN: 14664

American (AMR) AF: 0.438 AC: 10670 AN: 24384

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 5612 AN: 14844

East Asian (EAS) AF: 0.651 AC: 20206 AN: 31028

South Asian (SAS) AF: 0.364 AC: 17501 AN: 48072

European-Finnish (FIN) AF: 0.455 AC: 13475 AN: 29592

Middle Eastern (MID) AF: 0.412 AC: 1450 AN: 3522

European-Non Finnish (NFE) AF: 0.416 AC: 131523 AN: 316252

Other (OTH) AF: 0.412 AC: 11373 AN: 27628

GnomAD4 genome AF: 0.369 AC: 56106 AN: 152166 Hom.: 11394 Cov.: 34 AF XY: 0.372 AC XY: 27699 AN XY: 74390

African (AFR) AF: 0.201 AC: 8338 AN: 41520

American (AMR) AF: 0.424 AC: 6472 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3474 AN: 5176

South Asian (SAS) AF: 0.362 AC: 1748 AN: 4824

European-Finnish (FIN) AF: 0.453 AC: 4792 AN: 10582

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28619 AN: 67994

Other (OTH) AF: 0.386 AC: 815 AN: 2114

Alfa AF: 0.397 Hom.: 6467

Bravo AF: 0.361

Asia WGS AF: 0.458 AC: 1589 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.49
PhyloP100		0.11
PromoterAI		0.0025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2245168; hg19: chr10-81921918; COSMIC: COSV55417350; COSMIC: COSV55417350;