chr11-21932141-T-C

Variant names:

• chr11-21932141-T-C
• rs324175
• ENST00000648804.1:n.270-50825T>C

Variant summary

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

The ENST00000648804.1(ANO5):​n.270-50825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,034 control chromosomes in the GnomAD database, including 53,371 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. The gene ANO5 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.83 (53371 hom., cov: 31)
• Consequence: ANO5 ENST00000648804.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 2 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):

• gnathodiaphyseal dysplasia

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

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2L

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

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

LOC102723370 (HGNC:):

ACMG classification

Specifications for ANO5 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	ENST00000648804.1		n.270-50825T>C		intron	N/A
	ANO5	ENST00000682428.1		n.197-208T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126732 AN: 151916 Hom.: 53328 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.834 AC: 126831 AN: 152034 Hom.: 53371 Cov.: 31 AF XY: 0.835 AC XY: 62039 AN XY: 74302

African (AFR) AF: 0.721 AC: 29895 AN: 41444

American (AMR) AF: 0.832 AC: 12679 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2870 AN: 3470

East Asian (EAS) AF: 0.931 AC: 4802 AN: 5156

South Asian (SAS) AF: 0.858 AC: 4133 AN: 4818

European-Finnish (FIN) AF: 0.874 AC: 9240 AN: 10578

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60332 AN: 68016

Other (OTH) AF: 0.837 AC: 1768 AN: 2112

Alfa AF: 0.848 Hom.: 9264

Bravo AF: 0.827

Asia WGS AF: 0.849 AC: 2952 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	1.9
DANN	Benign	0.36
PhyloP100		-0.63

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs324175;

hg19: chr11-21953687;