10-80156034-T-C

Variant names:

• chr10-80156034-T-C
• rs2789687
• NM_145868.2:c.1459-122A>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.1459-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,006,106 control chromosomes in the GnomAD database, including 450,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (66661 hom., cov: 33)
  • Exomes 𝑓: 0.95 (384122 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.141
• 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=-0.9).
• BP6: Variant 10-80156034-T-C is Benign according to our data. Variant chr10-80156034-T-C is described in ClinVar as [Benign]. Clinvar id is 1248519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.1459-122A>G		intron_variant	Intron 15 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.1459-122A>G		intron_variant	Intron 15 of 15	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142367 AN: 152176 Hom.: 66603 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.955

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.960

GnomAD4 exome AF: 0.948 AC: 809683 AN: 853812 Hom.: 384122 AF XY: 0.949 AC XY: 417929 AN XY: 440556

African (AFR) AF: 0.910 AC: 19164 AN: 21070

American (AMR) AF: 0.976 AC: 34989 AN: 35856

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 17341 AN: 18800

East Asian (EAS) AF: 1.00 AC: 36410 AN: 36416

South Asian (SAS) AF: 0.964 AC: 62152 AN: 64506

European-Finnish (FIN) AF: 0.941 AC: 44667 AN: 47466

Middle Eastern (MID) AF: 0.961 AC: 4085 AN: 4250

European-Non Finnish (NFE) AF: 0.944 AC: 553066 AN: 585646

Other (OTH) AF: 0.950 AC: 37809 AN: 39802

GnomAD4 genome AF: 0.936 AC: 142481 AN: 152294 Hom.: 66661 Cov.: 33 AF XY: 0.936 AC XY: 69716 AN XY: 74466

African (AFR) AF: 0.909 AC: 37777 AN: 41556

American (AMR) AF: 0.955 AC: 14600 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3223 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5179 AN: 5180

South Asian (SAS) AF: 0.971 AC: 4682 AN: 4824

European-Finnish (FIN) AF: 0.938 AC: 9965 AN: 10622

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.939 AC: 63886 AN: 68030

Other (OTH) AF: 0.961 AC: 2033 AN: 2116

Alfa AF: 0.938 Hom.: 25487

Bravo AF: 0.939

Asia WGS AF: 0.982 AC: 3414 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	-0.90
CADD	Benign	7.4
DANN	Benign	0.54
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2789687; hg19: chr10-81915790;