10-80171685-C-T

Variant names:

• chr10-80171685-C-T
• rs2573351
• NM_145868.2:c.56-770G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278409.2(ANXA11):​c.-117G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 985,278 control chromosomes in the GnomAD database, including 101,753 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 0.49 (18874 hom., cov: 33)
  • Exomes 𝑓: 0.44 (82879 hom.)
• Consequence: ANXA11 NM_001278409.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278409.2. 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.56-770G>A		intron	N/A	NP_665875.1	P50995-1
	ANXA11	NM_001278409.2		c.-117G>A		5_prime_UTR	Exon 4 of 17	NP_001265338.1	P50995-2
	ANXA11	NM_001157.3		c.56-770G>A		intron	N/A	NP_001148.1	P50995-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA11	ENST00000422982.8	TSL:1 MANE Select	c.56-770G>A		intron	N/A	ENSP00000404412.2	P50995-1
	ANXA11	ENST00000372231.7	TSL:1	c.56-770G>A		intron	N/A	ENSP00000361305.3	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.56-770G>A		intron	N/A	ENSP00000398610.1	P50995-1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73840 AN: 152018 Hom.: 18835 Cov.: 33

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.444 AC: 369929 AN: 833142 Hom.: 82879 Cov.: 32 AF XY: 0.445 AC XY: 171045 AN XY: 384746

African (AFR) AF: 0.651 AC: 10271 AN: 15786

American (AMR) AF: 0.299 AC: 295 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 2612 AN: 5152

East Asian (EAS) AF: 0.312 AC: 1132 AN: 3630

South Asian (SAS) AF: 0.418 AC: 6888 AN: 16460

European-Finnish (FIN) AF: 0.447 AC: 127 AN: 284

Middle Eastern (MID) AF: 0.456 AC: 739 AN: 1622

European-Non Finnish (NFE) AF: 0.440 AC: 335506 AN: 761918

Other (OTH) AF: 0.453 AC: 12359 AN: 27304

GnomAD4 genome AF: 0.486 AC: 73930 AN: 152136 Hom.: 18874 Cov.: 33 AF XY: 0.481 AC XY: 35791 AN XY: 74376

African (AFR) AF: 0.636 AC: 26383 AN: 41502

American (AMR) AF: 0.365 AC: 5586 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1653 AN: 5158

South Asian (SAS) AF: 0.400 AC: 1931 AN: 4824

European-Finnish (FIN) AF: 0.453 AC: 4794 AN: 10586

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30271 AN: 67986

Other (OTH) AF: 0.457 AC: 966 AN: 2114

Alfa AF: 0.465 Hom.: 6387

Bravo AF: 0.484

Asia WGS AF: 0.405 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.2
DANN	Benign	0.74
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs2573351; hg19: chr10-81931441;