rs150412089

chr11-22255323-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_213599.3(ANO5):c.1181-48T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,456,584 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (9 hom., cov: 32)
  • Exomes 𝑓: 0.012 (121 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.580

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-22255323-T-A is Benign according to our data. Variant chr11-22255323-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 263310.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 = 0.00751 (1143/152120) while in subpopulation NFE AF= 0.0121 (824/67986). AF 95% confidence interval is 0.0114. There are 9 homozygotes in gnomad4. There are 504 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO5	NM_213599.3	c.1181-48T>A		intron_variant		ENST00000324559.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO5	ENST00000324559.9	c.1181-48T>A		intron_variant		1	NM_213599.3	P2

Frequencies

GnomAD3 genomes AF: 0.00752 AC: 1143 AN: 152002 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00754

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00445

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00747 AC: 1184 AN: 158520 Hom.: 6 AF XY: 0.00747 AC XY: 658 AN XY: 88028

Gnomad AFR exome AF: 0.00235

Gnomad AMR exome AF: 0.00570

Gnomad ASJ exome AF: 0.00125

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00174

Gnomad FIN exome AF: 0.00497

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.00883

GnomAD4 exome AF: 0.0119 AC: 15566 AN: 1304464 Hom.: 121 Cov.: 24 AF XY: 0.0116 AC XY: 7535 AN XY: 648860

Gnomad4 AFR exome AF: 0.00220

Gnomad4 AMR exome AF: 0.00573

Gnomad4 ASJ exome AF: 0.00163

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00184

Gnomad4 FIN exome AF: 0.00644

Gnomad4 NFE exome AF: 0.0141

Gnomad4 OTH exome AF: 0.00930

GnomAD4 genome AF: 0.00751 AC: 1143 AN: 152120 Hom.: 9 Cov.: 32 AF XY: 0.00678 AC XY: 504 AN XY: 74390

Gnomad4 AFR AF: 0.00287

Gnomad4 AMR AF: 0.00753

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00445

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00800 Hom.: 2

Bravo AF: 0.00753

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.5
Dann	Benign	0.37

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: rs150412089; hg19: chr11-22276869;