rs7067644

Variant names:

• chr10-80164489-G-A
• rs7067644
• NM_145868.2:c.859-346C>T

Variant summary

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

The NM_145868.2(ANXA11):​c.859-346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,972 control chromosomes in the GnomAD database, including 13,965 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 0.42 (13965 hom., cov: 33)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 8 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: Genomics England PanelApp, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.859-346C>T		intron_variant	Intron 8 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.859-346C>T		intron_variant	Intron 8 of 15	1	NM_145868.2	ENSP00000404412.2
ANXA11	ENST00000372231.7	c.859-346C>T		intron_variant	Intron 7 of 14	1		ENSP00000361305.3
ANXA11	ENST00000438331.5	c.859-346C>T		intron_variant	Intron 9 of 16	1		ENSP00000398610.1
ANXA11	ENST00000265447.8	c.760-346C>T		intron_variant	Intron 7 of 14	5		ENSP00000265447.5

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63657 AN: 151854 Hom.: 13937 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.419 AC: 63734 AN: 151972 Hom.: 13965 Cov.: 33 AF XY: 0.416 AC XY: 30872 AN XY: 74270

African (AFR) AF: 0.541 AC: 22413 AN: 41430

American (AMR) AF: 0.320 AC: 4888 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1488 AN: 3464

East Asian (EAS) AF: 0.312 AC: 1613 AN: 5174

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4818

European-Finnish (FIN) AF: 0.393 AC: 4141 AN: 10528

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26064 AN: 67968

Other (OTH) AF: 0.415 AC: 877 AN: 2114

Alfa AF: 0.392 Hom.: 9350

Bravo AF: 0.420

Asia WGS AF: 0.363 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.66
PhyloP100		-0.77
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: rs7067644; hg19: chr10-81924245;