Genetic Variant ANO5:n.270-33963C>T (chr11-21949003-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.390

Publications

0 publications found

Variant links:

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)

ANO5 links:

LOC102723370 (HGNC:):

LOC102723370 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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	Effect	Exon rank
LOC102723370	XR_007062617.1 link	n.176+4092C>T	intron_variant	Intron 1 of 5
LOC102723370	XR_007062618.1 link	n.114-33963C>T	intron_variant	Intron 2 of 4
LOC102723370	XR_007062619.1 link	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 link	n.270-33963C>T		intron_variant	Intron 3 of 23
ANO5	ENST00000682428.1 link	n.802+4092C>T		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26102

AN:

151926

Hom.:

2314

Cov.:

show subpopulations

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.:

AF XY:

0.173

AC XY:

12840

AN XY:

74302

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11835

AN:

67976

Other (OTH)

AF:

0.173

AC:

365

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1062

2125

3187

4250

5312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.58

PhyloP100

-0.39

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over