11-22250927-A-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_213599.3(ANO5):c.1120-24A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,609,586 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.021 ( 50 hom., cov: 32)

Exomes 𝑓: 0.031 ( 836 hom. )

Consequence

ANO5
NM_213599.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.386

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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-22250927-A-T is Benign according to our data. Variant chr11-22250927-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 263308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0206 (3138/152140) while in subpopulation NFE AF= 0.0339 (2306/67984). AF 95% confidence interval is 0.0328. There are 50 homozygotes in gnomad4. There are 1457 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO5	NM_213599.3 link	c.1120-24A>T		intron_variant	Intron 11 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.1120-24A>T		intron_variant	Intron 11 of 21	1	NM_213599.3	ENSP00000315371.9		Q75V66

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3138

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00727

Gnomad AMI

AF:

0.0703

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0339

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.0190

AC:

4758

AN:

250078

Hom.:

AF XY:

0.0189

AC XY:

2559

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.00610

Gnomad AMR exome

AF:

0.00736

Gnomad ASJ exome

AF:

0.00677

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.0245

Gnomad NFE exome

AF:

0.0323

Gnomad OTH exome

AF:

0.0197

GnomAD4 exome

AF:

0.0307

AC:

44685

AN:

1457446

Hom.:

836

Cov.:

AF XY:

0.0294

AC XY:

21296

AN XY:

725336

show subpopulations

Gnomad4 AFR exome

AF:

0.00536

Gnomad4 AMR exome

AF:

0.00812

Gnomad4 ASJ exome

AF:

0.00571

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00157

Gnomad4 FIN exome

AF:

0.0258

Gnomad4 NFE exome

AF:

0.0369

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0206

AC:

3138

AN:

152140

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1457

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00725

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0240

Gnomad4 NFE

AF:

0.0339

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 16, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Gnathodiaphyseal dysplasia

Benign:1

Dec 05, 2021

Genome-Nilou Lab

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

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

DANN

Benign

0.56

La Branchor

0.48

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

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