dbSNP rs12225197: ANO5:n.68+16134G>A (chr11-21798860-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000664026.1(ANO5):n.68+16134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 151,962 control chromosomes in the GnomAD database, including 227 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 0.022 ( 227 hom., cov: 32)

Consequence

ANO5
ENST00000664026.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.491

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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC102723370	XR_007062619.1 link	n.649+3956G>A	intron_variant	Intron 2 of 4
LOC102723370	XR_007062621.1 link	n.199+3956G>A	intron_variant	Intron 2 of 2
LOC102723370	XR_931109.3 link	n.200-1901G>A	intron_variant	Intron 2 of 2
LOC102723370	XR_931110.3 link	n.199+3956G>A	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ANO5	ENST00000664026.1 link	n.68+16134G>A	intron_variant	Intron 1 of 2
ANO5	ENST00000682428.1 link	n.196+3956G>A	intron_variant	Intron 2 of 6
ANO5	ENST00000683812.1 link	n.187-1901G>A	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3394

AN:

151844

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0988

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.0957

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.0215

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

GnomAD4 genome

AF:

0.0223

AC:

3390

AN:

151962

Hom.:

227

Cov.:

AF XY:

0.0265

AC XY:

1972

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.00332

AC:

138

AN:

41506

American (AMR)

AF:

0.0989

AC:

1506

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3462

East Asian (EAS)

AF:

0.194

AC:

997

AN:

5150

South Asian (SAS)

AF:

0.0946

AC:

457

AN:

4832

European-Finnish (FIN)

AF:

0.0126

AC:

134

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00159

AC:

108

AN:

67860

Other (OTH)

AF:

0.0213

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0108

Hom.:

285

Bravo

AF:

0.0294

Asia WGS

AF:

0.119

AC:

414

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.9

(source)

DANN

Benign

0.32

PhyloP100

0.49

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