rs11026318

Variant names:

• chr11-21875334-C-T
• rs11026318
• ENST00000648804.1:n.269+18923C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648804.1(ANO5):​n.269+18923C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,078 control chromosomes in the GnomAD database, including 2,784 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 0.16 (2784 hom., cov: 32)
• Consequence: ANO5 ENST00000648804.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 7 publications found

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]

ANO5 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• gnathodiaphyseal dysplasia

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive limb-girdle muscular dystrophy type 2L

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Miyoshi muscular dystrophy 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LOC102723370 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102723370	XR_007062618.1	n.113+18923C>T		intron_variant	Intron 2 of 4
LOC102723370	XR_007062619.1	n.649+80430C>T		intron_variant	Intron 2 of 4
LOC102723370	XR_931110.3	n.199+80430C>T		intron_variant	Intron 2 of 4
LOC102723370	XR_931111.3	n.113+18923C>T		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000648804.1	n.269+18923C>T		intron_variant	Intron 3 of 23
ANO5	ENST00000682428.1	n.197-57015C>T		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24321 AN: 151960 Hom.: 2776 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0728

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.160 AC: 24377 AN: 152078 Hom.: 2784 Cov.: 32 AF XY: 0.163 AC XY: 12099 AN XY: 74360

African (AFR) AF: 0.292 AC: 12107 AN: 41450

American (AMR) AF: 0.248 AC: 3786 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3472

East Asian (EAS) AF: 0.176 AC: 906 AN: 5158

South Asian (SAS) AF: 0.127 AC: 610 AN: 4822

European-Finnish (FIN) AF: 0.120 AC: 1274 AN: 10600

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0728 AC: 4950 AN: 67994

Other (OTH) AF: 0.150 AC: 315 AN: 2104

Alfa AF: 0.105 Hom.: 4972

Bravo AF: 0.180

Asia WGS AF: 0.166 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.23
PhyloP100		-0.77

Splicing

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

Other links and lift over

dbSNP: rs11026318; hg19: chr11-21896880;