11-22186181-A-C

Position:

• chr11-22186181-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648804.1(ANO5):​n.545-17623A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,976 control chromosomes in the GnomAD database, including 11,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (11040 hom., cov: 32)
• Consequence: ANO5 ENST00000648804.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000648804.1	n.545-17623A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48944 AN: 151860 Hom.: 11013 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.323 AC: 49019 AN: 151976 Hom.: 11040 Cov.: 32 AF XY: 0.324 AC XY: 24032 AN XY: 74284

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.270

Alfa AF: 0.194 Hom.: 2377

Bravo AF: 0.344

Asia WGS AF: 0.389 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10833716; hg19: chr11-22207727;