dbSNP rs114582774: ANO5:c.1181-21T>A (chr11-22255350-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_213599.3(ANO5):c.1181-21T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,538,260 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). The gene ANO5 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.0095 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 31 hom. )

Consequence

ANO5
NM_213599.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0550

Publications

1 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):

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)

ANO5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_213599.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

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

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-22255350-T-A is Benign according to our data. Variant chr11-22255350-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 263309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00947 (1441/152238) while in subpopulation AFR AF = 0.0325 (1349/41554). AF 95% confidence interval is 0.031. There are 22 homozygotes in GnomAd4. There are 640 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213599.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO5	NM_213599.3	MANE Select	c.1181-21T>A	intron	N/A	NP_998764.1	Q75V66
ANO5	NM_001142649.2		c.1178-21T>A	intron	N/A	NP_001136121.1
ANO5	NM_001410963.1		c.1139-21T>A	intron	N/A	NP_001397892.1	A0A804HL91

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO5	ENST00000324559.9	TSL:1 MANE Select	c.1181-21T>A	intron	N/A	ENSP00000315371.9	Q75V66
ANO5	ENST00000682341.1		c.1139-21T>A	intron	N/A	ENSP00000508251.1	A0A804HL91
ANO5	ENST00000684663.1		c.1136-21T>A	intron	N/A	ENSP00000508009.1	A0A804HKP2

Frequencies

GnomAD3 genomes

AF:

0.00945

AC:

1437

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00280

AC:

579

AN:

206802

AF XY:

0.00229

show subpopulations

Gnomad AFR exome

AF:

0.0381

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.0000509

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00110

AC:

1523

AN:

1386022

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

690

AN XY:

688970

show subpopulations

African (AFR)

AF:

0.0370

AC:

1121

AN:

30272

American (AMR)

AF:

0.00181

AC:

AN:

35940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24026

East Asian (EAS)

AF:

0.0000522

AC:

AN:

38324

South Asian (SAS)

AF:

0.000396

AC:

AN:

73162

European-Finnish (FIN)

AF:

0.0000605

AC:

AN:

49626

Middle Eastern (MID)

AF:

0.00285

AC:

AN:

5256

European-Non Finnish (NFE)

AF:

0.000114

AC:

122

AN:

1072338

Other (OTH)

AF:

0.00291

AC:

166

AN:

57078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

148

222

296

370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00947

AC:

1441

AN:

152238

Hom.:

Cov.:

AF XY:

0.00860

AC XY:

640

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0325

AC:

1349

AN:

41554

American (AMR)

AF:

0.00386

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68022

Other (OTH)

AF:

0.00853

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

141

211

282

352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00138

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.00927

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.48

(source)

DANN

Benign

0.29

PhyloP100

0.055

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over