rs2236556

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-80173034-T-C
• chr10-80173034-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145868.2(ANXA11):​c.-8-165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 605,178 control chromosomes in the GnomAD database, including 107,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31589 hom., cov: 34)
  • Exomes 𝑓: 0.57 (76358 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-80173034-T-C is Benign according to our data. Variant chr10-80173034-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

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>G		intron	N/A	NP_665875.1	P50995-1
	ANXA11	NM_001157.3		c.-8-165A>G		intron	N/A	NP_001148.1	P50995-1
	ANXA11	NM_001278407.2		c.-8-165A>G		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>G		intron	N/A	ENSP00000404412.2	P50995-1
	ANXA11	ENST00000372231.7	TSL:1	c.-8-165A>G		intron	N/A	ENSP00000361305.3	P50995-1
	ANXA11	ENST00000438331.5	TSL:1	c.-8-165A>G		intron	N/A	ENSP00000398610.1	P50995-1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96207 AN: 152058 Hom.: 31514 Cov.: 34

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.574 AC: 260165 AN: 453002 Hom.: 76358 Cov.: 5 AF XY: 0.576 AC XY: 137554 AN XY: 238676

African (AFR) AF: 0.796 AC: 9377 AN: 11774

American (AMR) AF: 0.554 AC: 10105 AN: 18242

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 8271 AN: 13390

East Asian (EAS) AF: 0.350 AC: 10111 AN: 28908

South Asian (SAS) AF: 0.632 AC: 29294 AN: 46348

European-Finnish (FIN) AF: 0.542 AC: 16257 AN: 30008

Middle Eastern (MID) AF: 0.590 AC: 1614 AN: 2734

European-Non Finnish (NFE) AF: 0.580 AC: 160042 AN: 275786

Other (OTH) AF: 0.585 AC: 15094 AN: 25812

GnomAD4 genome AF: 0.633 AC: 96340 AN: 152176 Hom.: 31589 Cov.: 34 AF XY: 0.629 AC XY: 46818 AN XY: 74392

African (AFR) AF: 0.804 AC: 33394 AN: 41538

American (AMR) AF: 0.578 AC: 8835 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2159 AN: 3472

East Asian (EAS) AF: 0.337 AC: 1739 AN: 5164

South Asian (SAS) AF: 0.641 AC: 3092 AN: 4826

European-Finnish (FIN) AF: 0.545 AC: 5771 AN: 10586

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39368 AN: 67982

Other (OTH) AF: 0.615 AC: 1301 AN: 2116

Alfa AF: 0.633 Hom.: 4004

Bravo AF: 0.641

Asia WGS AF: 0.560 AC: 1949 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.59
PhyloP100		0.082
PromoterAI		0.10	Neutral
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: rs2236556; hg19: chr10-81932790;