10-80173034-T-A

Variant names:

• chr10-80173034-T-A
• rs2236556
• NM_145868.2:c.-8-165A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145868.2(ANXA11):​c.-8-165A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 453,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAdExome4 at 8 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.-8-165A>T		intron	N/A	NP_665875.1	P50995-1
	ANXA11	NM_001157.3		c.-8-165A>T		intron	N/A	NP_001148.1	P50995-1
	ANXA11	NM_001278407.2		c.-8-165A>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.-8-165A>T		intron	N/A	ENSP00000404412.2	P50995-1
	ANXA11	ENST00000372231.7	TSL:1	c.-8-165A>T		intron	N/A	ENSP00000361305.3	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.-8-165A>T		intron	N/A	ENSP00000398610.1	P50995-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000176 AC: 8 AN: 453708 Hom.: 0 Cov.: 5 AF XY: 0.00000837 AC XY: 2 AN XY: 239048

African (AFR) AF: 0.00 AC: 0 AN: 11794

American (AMR) AF: 0.00 AC: 0 AN: 18282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13410

East Asian (EAS) AF: 0.00 AC: 0 AN: 28974

South Asian (SAS) AF: 0.00 AC: 0 AN: 46398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2738

European-Non Finnish (NFE) AF: 0.0000253 AC: 7 AN: 276206

Other (OTH) AF: 0.0000387 AC: 1 AN: 25856

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		0.082
PromoterAI		0.0025	Neutral

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: rs2236556; hg19: chr10-81932790;