11-22274548-CTTTTT-CTTTTTTT

Position:

• chr11-22274548-CTTTTT-CTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP6_Moderate BS2_Supporting

The ENST00000324559.9(ANO5):​c.2236-11_2236-10dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,266,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: ANO5 ENST00000324559.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.693

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 Likely_benign. Variant got -3 ACMG points.

• BP6: Variant 11-22274548-C-CTT is Benign according to our data. Variant chr11-22274548-C-CTT is described in ClinVar as [Benign]. Clinvar id is 592736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 34 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO5	NM_213599.3	c.2236-11_2236-10dup		intron_variant		ENST00000324559.9	NP_998764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9	c.2236-11_2236-10dup		intron_variant		1	NM_213599.3	ENSP00000315371	P2

Frequencies

GnomAD3 genomes AF: 0.000231 AC: 34 AN: 147070 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000744

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000314

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000422

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000304 AC: 35 AN: 115060 Hom.: 0 AF XY: 0.000371 AC XY: 23 AN XY: 61940

Gnomad AFR exome AF: 0.000296

Gnomad AMR exome AF: 0.0000861

Gnomad ASJ exome AF: 0.000309

Gnomad EAS exome AF: 0.000155

Gnomad SAS exome AF: 0.000180

Gnomad FIN exome AF: 0.000292

Gnomad NFE exome AF: 0.000403

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000353 AC: 395 AN: 1119048 Hom.: 0 Cov.: 0 AF XY: 0.000353 AC XY: 195 AN XY: 552904

Gnomad4 AFR exome AF: 0.000116

Gnomad4 AMR exome AF: 0.000109

Gnomad4 ASJ exome AF: 0.0000547

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.0000647

Gnomad4 FIN exome AF: 0.000173

Gnomad4 NFE exome AF: 0.000409

Gnomad4 OTH exome AF: 0.000433

GnomAD4 genome AF: 0.000231 AC: 34 AN: 147070 Hom.: 0 Cov.: 27 AF XY: 0.000321 AC XY: 23 AN XY: 71620

Gnomad4 AFR AF: 0.0000744

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000314

Gnomad4 NFE AF: 0.000422

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72105710; hg19: chr11-22296094;