NM_145868.2:c.1458+77C>T

Variant names:

• chr10-80157564-G-A
• rs12775374
• NM_145868.2:c.1458+77C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145868.2(ANXA11):​c.1458+77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,564,900 control chromosomes in the GnomAD database, including 1,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (56 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1163 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Ambry Genetics
• inclusion body myopathy and brain white matter abnormalities

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-80157564-G-A is Benign according to our data. Variant chr10-80157564-G-A is described in ClinVar as Benign. ClinVar VariationId is 1693167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0252 (3834/152208) while in subpopulation NFE AF = 0.0391 (2656/68006). AF 95% confidence interval is 0.0378. There are 56 homozygotes in GnomAd4. There are 1846 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3834 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	NM_145868.2	MANE Select	c.1458+77C>T		intron	N/A	NP_665875.1	P50995-1
	ANXA11	NM_001157.3		c.1458+77C>T		intron	N/A	NP_001148.1	P50995-1
	ANXA11	NM_001278407.2		c.1458+77C>T		intron	N/A	NP_001265336.1	Q5T0G8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.1458+77C>T		intron	N/A	ENSP00000404412.2	P50995-1
	ANXA11	ENST00000372231.7	TSL:1	c.1458+77C>T		intron	N/A	ENSP00000361305.3	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.1458+77C>T		intron	N/A	ENSP00000398610.1	P50995-1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3836 AN: 152090 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.00662

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.0379 AC: 53517 AN: 1412692 Hom.: 1163 Cov.: 31 AF XY: 0.0381 AC XY: 26511 AN XY: 696542

African (AFR) AF: 0.00569 AC: 185 AN: 32524

American (AMR) AF: 0.0150 AC: 606 AN: 40518

Ashkenazi Jewish (ASJ) AF: 0.0341 AC: 777 AN: 22802

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39144

South Asian (SAS) AF: 0.0406 AC: 3190 AN: 78504

European-Finnish (FIN) AF: 0.0298 AC: 1514 AN: 50768

Middle Eastern (MID) AF: 0.0472 AC: 262 AN: 5554

European-Non Finnish (NFE) AF: 0.0414 AC: 44944 AN: 1084568

Other (OTH) AF: 0.0349 AC: 2035 AN: 58310

GnomAD4 genome AF: 0.0252 AC: 3834 AN: 152208 Hom.: 56 Cov.: 32 AF XY: 0.0248 AC XY: 1846 AN XY: 74420

African (AFR) AF: 0.00660 AC: 274 AN: 41530

American (AMR) AF: 0.0162 AC: 248 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.0382 AC: 184 AN: 4820

European-Finnish (FIN) AF: 0.0268 AC: 284 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0391 AC: 2656 AN: 68006

Other (OTH) AF: 0.0223 AC: 47 AN: 2108

Alfa AF: 0.0318 Hom.: 13

Bravo AF: 0.0248

Asia WGS AF: 0.0150 AC: 52 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inclusion body myopathy and brain white matter abnormalities (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		-0.062
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs12775374; hg19: chr10-81917320;