rs72982041

chr11-22262094-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_213599.3(ANO5):c.1631-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,606,742 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (12 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.161

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-22262094-G-A is Benign according to our data. Variant chr11-22262094-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 491 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO5	NM_213599.3	c.1631-35G>A		intron_variant		ENST00000324559.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO5	ENST00000324559.9	c.1631-35G>A		intron_variant		1	NM_213599.3	P2
	ENST00000526935.1	n.88+75C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 491 AN: 152134 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00519

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00465

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00354 AC: 883 AN: 249610 Hom.: 1 AF XY: 0.00348 AC XY: 470 AN XY: 135016

Gnomad AFR exome AF: 0.000740

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00573

Gnomad NFE exome AF: 0.00575

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00358 AC: 5211 AN: 1454490 Hom.: 12 Cov.: 29 AF XY: 0.00357 AC XY: 2586 AN XY: 724010

Gnomad4 AFR exome AF: 0.000661

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00207

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000581

Gnomad4 FIN exome AF: 0.00655

Gnomad4 NFE exome AF: 0.00401

Gnomad4 OTH exome AF: 0.00325

GnomAD4 genome AF: 0.00322 AC: 490 AN: 152252 Hom.: 3 Cov.: 32 AF XY: 0.00306 AC XY: 228 AN XY: 74448

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00519

Gnomad4 NFE AF: 0.00465

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00373 Hom.: 0

Bravo AF: 0.00326

Asia WGS AF: 0.000289 AC: 2 AN: 3478

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

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 21, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.44

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: rs72982041; hg19: chr11-22283640;