Genetic Variant ANO5:c.2236-13_2236-10delTTTT (chr11-22274548-CTTTT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_213599.3(ANO5):c.2236-13_2236-10delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,266,820 control chromosomes in the GnomAD database, including 7,620 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 965 hom., cov: 27)

Exomes 𝑓: 0.12 ( 6655 hom. )

Consequence

ANO5
NM_213599.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.693

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-22274548-CTTTT-C is Benign according to our data. Variant chr11-22274548-CTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 96678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22274548-CTTTT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO5	NM_213599.3 link	c.2236-13_2236-10delTTTT		intron_variant	Intron 19 of 21	ENST00000324559.9	NP_998764.1	Q75V66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9 link	c.2236-20_2236-17delTTTT		intron_variant	Intron 19 of 21	1	NM_213599.3	ENSP00000315371.9		Q75V66

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16140

AN:

147036

Hom.:

962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.0673

Gnomad ASJ

AF:

0.0653

Gnomad EAS

AF:

0.00138

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0795

Gnomad MID

AF:

0.0903

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0968

GnomAD3 exomes

AF:

0.160

AC:

18417

AN:

115060

Hom.:

966

AF XY:

0.164

AC XY:

10132

AN XY:

61940

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.155

Gnomad EAS exome

AF:

0.00155

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.117

AC:

131055

AN:

1119710

Hom.:

6655

AF XY:

0.117

AC XY:

64590

AN XY:

553250

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.0622

Gnomad4 ASJ exome

AF:

0.0835

Gnomad4 EAS exome

AF:

0.000735

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0877

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.110

AC:

16149

AN:

147110

Hom.:

965

Cov.:

AF XY:

0.107

AC XY:

7695

AN XY:

71694

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.0672

Gnomad4 ASJ

AF:

0.0653

Gnomad4 EAS

AF:

0.00139

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.0795

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.0956

Alfa

AF:

0.0424

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 17, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Miyoshi muscular dystrophy 3

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Gnathodiaphyseal dysplasia

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2L

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

11-22274548-CTTTTT-CT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over