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.

• 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):

• 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)

LOC102723370 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102723370	XR_007062617.1	n.176+4092C>T		intron_variant	Intron 1 of 5
LOC102723370	XR_007062618.1	n.114-33963C>T		intron_variant	Intron 2 of 4
LOC102723370	XR_007062619.1	n.650-33963C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000648804.1	n.270-33963C>T		intron_variant	Intron 3 of 23
ANO5	ENST00000682428.1	n.802+4092C>T		intron_variant	Intron 5 of 6

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 v4.3

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

Other links and lift over

dbSNP: rs12295951; hg19: chr11-21970549;