chr10-80157873-T-C

Variant names:

• chr10-80157873-T-C
• rs12767142
• NM_145868.2:c.1335+94A>G

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.1335+94A>G 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 1,589,450 control chromosomes in the GnomAD database, including 1,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (55 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1182 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.181
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-80157873-T-C is Benign according to our data. Variant chr10-80157873-T-C is described in ClinVar as [Benign]. Clinvar id is 1693168.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 (3828/152074) while in subpopulation NFE AF = 0.0391 (2654/67956). AF 95% confidence interval is 0.0378. There are 55 homozygotes in GnomAd4. There are 1838 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3828 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.1335+94A>G		intron_variant	Intron 14 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.1335+94A>G		intron_variant	Intron 14 of 15	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3830 AN: 151956 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00665

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.0378 AC: 54368 AN: 1437376 Hom.: 1182 Cov.: 28 AF XY: 0.0380 AC XY: 27135 AN XY: 713662

African (AFR) AF: 0.00569 AC: 187 AN: 32884

American (AMR) AF: 0.0150 AC: 654 AN: 43678

Ashkenazi Jewish (ASJ) AF: 0.0344 AC: 866 AN: 25144

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39408

South Asian (SAS) AF: 0.0405 AC: 3414 AN: 84354

European-Finnish (FIN) AF: 0.0301 AC: 1592 AN: 52944

Middle Eastern (MID) AF: 0.0478 AC: 264 AN: 5526

European-Non Finnish (NFE) AF: 0.0414 AC: 45320 AN: 1094050

Other (OTH) AF: 0.0348 AC: 2067 AN: 59388

GnomAD4 genome AF: 0.0252 AC: 3828 AN: 152074 Hom.: 55 Cov.: 32 AF XY: 0.0247 AC XY: 1838 AN XY: 74332

African (AFR) AF: 0.00663 AC: 275 AN: 41494

American (AMR) AF: 0.0162 AC: 247 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3464

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5152

South Asian (SAS) AF: 0.0381 AC: 183 AN: 4808

European-Finnish (FIN) AF: 0.0266 AC: 282 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0391 AC: 2654 AN: 67956

Other (OTH) AF: 0.0223 AC: 47 AN: 2110

Alfa AF: 0.0321 Hom.: 11

Bravo AF: 0.0248

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inclusion body myopathy and brain white matter abnormalities Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.76
PhyloP100		-0.18
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: rs12767142; hg19: chr10-81917629;