rs114582774

Variant names:

• chr11-22255350-T-A
• rs114582774
• NM_213599.3:c.1181-21T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-22255350-T-A
• chr11-22255350-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_213599.3(ANO5):​c.1181-21T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,538,260 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (31 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0550
• Publications: 1 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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-22255350-T-A is Benign according to our data. Variant chr11-22255350-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 263309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00947 (1441/152238) while in subpopulation AFR AF = 0.0325 (1349/41554). AF 95% confidence interval is 0.031. There are 22 homozygotes in GnomAd4. There are 640 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213599.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	NM_213599.3	MANE Select	c.1181-21T>A		intron	N/A	NP_998764.1
	ANO5	NM_001142649.2		c.1178-21T>A		intron	N/A	NP_001136121.1
	ANO5	NM_001410963.1		c.1139-21T>A		intron	N/A	NP_001397892.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO5	ENST00000324559.9	TSL:1 MANE Select	c.1181-21T>A		intron	N/A	ENSP00000315371.9
	ANO5	ENST00000682341.1		c.1139-21T>A		intron	N/A	ENSP00000508251.1
	ANO5	ENST00000684663.1		c.1136-21T>A		intron	N/A	ENSP00000508009.1

Frequencies

GnomAD3 genomes AF: 0.00945 AC: 1437 AN: 152120 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00387

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00280 AC: 579 AN: 206802 AF XY: 0.00229

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.00141

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000134

Gnomad FIN exome AF: 0.0000509

Gnomad NFE exome AF: 0.000187

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00110 AC: 1523 AN: 1386022 Hom.: 31 Cov.: 28 AF XY: 0.00100 AC XY: 690 AN XY: 688970

African (AFR) AF: 0.0370 AC: 1121 AN: 30272

American (AMR) AF: 0.00181 AC: 65 AN: 35940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24026

East Asian (EAS) AF: 0.0000522 AC: 2 AN: 38324

South Asian (SAS) AF: 0.000396 AC: 29 AN: 73162

European-Finnish (FIN) AF: 0.0000605 AC: 3 AN: 49626

Middle Eastern (MID) AF: 0.00285 AC: 15 AN: 5256

European-Non Finnish (NFE) AF: 0.000114 AC: 122 AN: 1072338

Other (OTH) AF: 0.00291 AC: 166 AN: 57078

GnomAD4 genome AF: 0.00947 AC: 1441 AN: 152238 Hom.: 22 Cov.: 32 AF XY: 0.00860 AC XY: 640 AN XY: 74446

African (AFR) AF: 0.0325 AC: 1349 AN: 41554

American (AMR) AF: 0.00386 AC: 59 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10580

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.00138 Hom.: 1

Bravo AF: 0.0114

Asia WGS AF: 0.00927 AC: 32 AN: 3468

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.29
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs114582774; hg19: chr11-22276896;