rs2573346

Positions:

• chr10-80158285-G-A
• chr10-80158285-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145868.2(ANXA11):​c.1277-260C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,040 control chromosomes in the GnomAD database, including 11,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11480 hom., cov: 32)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA11	NM_145868.2	c.1277-260C>T		intron_variant		ENST00000422982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA11	ENST00000422982.8	c.1277-260C>T		intron_variant		1	NM_145868.2	P2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55930 AN: 151922 Hom.: 11478 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.368 AC: 55920 AN: 152040 Hom.: 11480 Cov.: 32 AF XY: 0.371 AC XY: 27555 AN XY: 74300

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.391

Alfa AF: 0.360 Hom.: 1509

Bravo AF: 0.356

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs2573346; hg19: chr10-81918041;