rs114582774

chr11-22255350-T-Achr11-22255350-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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 (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (31 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 263309.Status of the report is criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1437 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO5	NM_213599.3	c.1181-21T>A		intron_variant		ENST00000324559.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO5	ENST00000324559.9	c.1181-21T>A		intron_variant		1	NM_213599.3	P2

Frequencies

GnomAD3 genomes AF: 0.00945 AC: 1437 AN: 152120 Hom.: 22 Cov.: 32

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

GnomAD3 exomes AF: 0.00280 AC: 579 AN: 206802 Hom.: 12 AF XY: 0.00229 AC XY: 261 AN XY: 113966

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 SAS exome AF: 0.000619

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.: 31 Cov.: 28 AF XY: 0.00100 AC XY: 690 AN XY: 688970

Gnomad4 AFR exome AF: 0.0370

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000522

Gnomad4 SAS exome AF: 0.000396

Gnomad4 FIN exome AF: 0.0000605

Gnomad4 NFE exome AF: 0.000114

Gnomad4 OTH exome AF: 0.00291

GnomAD4 genome AF: 0.00947 AC: 1441 AN: 152238 Hom.: 22 Cov.: 32 AF XY: 0.00860 AC XY: 640 AN XY: 74446

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00138 Hom.: 1

Bravo AF: 0.0114

Asia WGS AF: 0.00927 AC: 32 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.48
Dann	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs114582774; hg19: chr11-22276896;