rs12767142

chr10-80157873-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 3830 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA11	NM_145868.2	c.1335+94A>G		intron_variant		ENST00000422982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA11	ENST00000422982.8	c.1335+94A>G		intron_variant		1	NM_145868.2	P2

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

Gnomad4 AFR exome AF: 0.00569

Gnomad4 AMR exome AF: 0.0150

Gnomad4 ASJ exome AF: 0.0344

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.0405

Gnomad4 FIN exome AF: 0.0301

Gnomad4 NFE exome AF: 0.0414

Gnomad4 OTH exome AF: 0.0348

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

Gnomad4 AFR AF: 0.00663

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0381

Gnomad4 FIN AF: 0.0266

Gnomad4 NFE AF: 0.0391

Gnomad4 OTH AF: 0.0223

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

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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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12767142; hg19: chr10-81917629;