rs12295951

Variant names:

• chr11-21949003-C-T
• rs12295951
• ENST00000648804.1:n.270-33963C>T

Variant summary

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

The ENST00000648804.1(ANO5):​n.270-33963C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,044 control chromosomes in the GnomAD database, including 2,313 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 0.17 (2313 hom., cov: 32)
• Consequence: ANO5 ENST00000648804.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 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.270-33963C>T		intron	N/A
	ANO5	ENST00000682428.1		n.802+4092C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26102 AN: 151926 Hom.: 2314 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.172 AC: 26114 AN: 152044 Hom.: 2313 Cov.: 32 AF XY: 0.173 AC XY: 12840 AN XY: 74302

African (AFR) AF: 0.193 AC: 7995 AN: 41476

American (AMR) AF: 0.119 AC: 1812 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3470

East Asian (EAS) AF: 0.0228 AC: 118 AN: 5174

South Asian (SAS) AF: 0.153 AC: 735 AN: 4812

European-Finnish (FIN) AF: 0.226 AC: 2380 AN: 10542

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11835 AN: 67976

Other (OTH) AF: 0.173 AC: 365 AN: 2108

Alfa AF: 0.172 Hom.: 1794

Bravo AF: 0.163

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.58
PhyloP100		-0.39

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: rs12295951;

hg19: chr11-21970549;