10-80173034-T-C

Variant names:

• chr10-80173034-T-C
• rs2236556
• NM_145868.2:c.-8-165A>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.-8-165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 605,178 control chromosomes in the GnomAD database, including 107,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31589 hom., cov: 34)
  • Exomes 𝑓: 0.57 (76358 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0820
• Publications: 4 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=-0.85).
• BP6: Variant 10-80173034-T-C is Benign according to our data. Variant chr10-80173034-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.-8-165A>G		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.-8-165A>G		intron_variant	Intron 2 of 15	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96207 AN: 152058 Hom.: 31514 Cov.: 34

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.574 AC: 260165 AN: 453002 Hom.: 76358 Cov.: 5 AF XY: 0.576 AC XY: 137554 AN XY: 238676

African (AFR) AF: 0.796 AC: 9377 AN: 11774

American (AMR) AF: 0.554 AC: 10105 AN: 18242

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 8271 AN: 13390

East Asian (EAS) AF: 0.350 AC: 10111 AN: 28908

South Asian (SAS) AF: 0.632 AC: 29294 AN: 46348

European-Finnish (FIN) AF: 0.542 AC: 16257 AN: 30008

Middle Eastern (MID) AF: 0.590 AC: 1614 AN: 2734

European-Non Finnish (NFE) AF: 0.580 AC: 160042 AN: 275786

Other (OTH) AF: 0.585 AC: 15094 AN: 25812

GnomAD4 genome AF: 0.633 AC: 96340 AN: 152176 Hom.: 31589 Cov.: 34 AF XY: 0.629 AC XY: 46818 AN XY: 74392

African (AFR) AF: 0.804 AC: 33394 AN: 41538

American (AMR) AF: 0.578 AC: 8835 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2159 AN: 3472

East Asian (EAS) AF: 0.337 AC: 1739 AN: 5164

South Asian (SAS) AF: 0.641 AC: 3092 AN: 4826

European-Finnish (FIN) AF: 0.545 AC: 5771 AN: 10586

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39368 AN: 67982

Other (OTH) AF: 0.615 AC: 1301 AN: 2116

Alfa AF: 0.633 Hom.: 4004

Bravo AF: 0.641

Asia WGS AF: 0.560 AC: 1949 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	-0.85
CADD	Benign	3.2
DANN	Benign	0.59
PhyloP100		0.082
PromoterAI		0.10	Neutral
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: rs2236556; hg19: chr10-81932790;