rs1079242

chr10-80157952-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145868.2(ANXA11):c.1335+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,612,348 control chromosomes in the GnomAD database, including 206,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15398 hom., cov: 31)
  • Exomes 𝑓: 0.51 (191164 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.512

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-80157952-A-G is Benign according to our data. Variant chr10-80157952-A-G is described in ClinVar as [Benign]. Clinvar id is 1244057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA11	NM_145868.2	c.1335+15T>C		intron_variant		ENST00000422982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA11	ENST00000422982.8	c.1335+15T>C		intron_variant		1	NM_145868.2	P2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65331 AN: 151860 Hom.: 15396 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.449

GnomAD3 exomes AF: 0.482 AC: 121237 AN: 251306 Hom.: 30321 AF XY: 0.481 AC XY: 65317 AN XY: 135814

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.518

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.574

Gnomad SAS exome AF: 0.371

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.507 AC: 740229 AN: 1460370 Hom.: 191164 Cov.: 35 AF XY: 0.503 AC XY: 365487 AN XY: 726640

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.432

Gnomad4 EAS exome AF: 0.589

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.430 AC: 65339 AN: 151978 Hom.: 15398 Cov.: 31 AF XY: 0.432 AC XY: 32052 AN XY: 74268

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.445

Alfa AF: 0.497 Hom.: 26774

Bravo AF: 0.417

Asia WGS AF: 0.434 AC: 1506 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Inclusion body myopathy and brain white matter abnormalities Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.33
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1079242; hg19: chr10-81917708; COSMIC: COSV55416414;