11-22186181-A-C

Variant names:

• chr11-22186181-A-C
• rs10833716
• ENST00000648804.1:n.545-17623A>C

Variant summary

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

The ENST00000648804.1(ANO5):​n.545-17623A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,976 control chromosomes in the GnomAD database, including 11,040 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 0.32 (11040 hom., cov: 32)
• Consequence: ANO5 ENST00000648804.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 3 publications found

Genes affected

ANO5 (HGNC:27337): (anoctamin 5) This gene encodes a member of the anoctamin family of transmembrane proteins. The encoded protein is likely a calcium activated chloride channel. Mutations in this gene have been associated with gnathodiaphyseal dysplasia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

ANO5 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• gnathodiaphyseal dysplasia

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive limb-girdle muscular dystrophy type 2L

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Miyoshi muscular dystrophy 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648804.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	ENST00000648804.1		n.545-17623A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48944 AN: 151860 Hom.: 11013 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.323 AC: 49019 AN: 151976 Hom.: 11040 Cov.: 32 AF XY: 0.324 AC XY: 24032 AN XY: 74284

African (AFR) AF: 0.631 AC: 26122 AN: 41420

American (AMR) AF: 0.319 AC: 4858 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2225 AN: 5160

South Asian (SAS) AF: 0.243 AC: 1171 AN: 4818

European-Finnish (FIN) AF: 0.198 AC: 2094 AN: 10570

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.165 AC: 11193 AN: 67972

Other (OTH) AF: 0.270 AC: 569 AN: 2110

Alfa AF: 0.260 Hom.: 7021

Bravo AF: 0.344

Asia WGS AF: 0.389 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10833716; hg19: chr11-22207727;