11-22274548-CTTTTT-CTTT

Variant names:

• chr11-22274548-CTT-C
• rs72105710
• NM_213599.3:c.2236-11_2236-10delTT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_213599.3(ANO5):​c.2236-11_2236-10delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,262,936 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 -1 ACMG points.

• BS2: High AC in GnomAdExome4 at 135 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 rank	MANE	Protein	UniProt
ANO5	NM_213599.3	c.2236-11_2236-10delTT		intron_variant	Intron 19 of 21	ENST00000324559.9	NP_998764.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147042 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000248

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000365 AC: 42 AN: 115060 Hom.: 0 AF XY: 0.000291 AC XY: 18 AN XY: 61940

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000345

Gnomad ASJ exome AF: 0.000927

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000539

Gnomad FIN exome AF: 0.000875

Gnomad NFE exome AF: 0.000336

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000121 AC: 135 AN: 1115894 Hom.: 0 AF XY: 0.000131 AC XY: 72 AN XY: 551376

Gnomad4 AFR exome AF: 0.0000388

Gnomad4 AMR exome AF: 0.000146

Gnomad4 ASJ exome AF: 0.000220

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.000341

Gnomad4 FIN exome AF: 0.000447

Gnomad4 NFE exome AF: 0.0000926

Gnomad4 OTH exome AF: 0.0000868

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 147042 Hom.: 0 Cov.: 27 AF XY: 0.0000279 AC XY: 2 AN XY: 71608

Gnomad4 AFR AF: 0.0000248

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs72105710; hg19: chr11-22296094;