11-70088078-C-T

Variant names:

• chr11-70088078-C-T
• rs542259870
• NM_018043.7:c.435C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_018043.7(ANO1):​c.435C>T​(p.Asp145Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000953 in 1,343,110 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00037 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: ANO1 NM_018043.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.251
• Publications: 0 publications found

Genes affected

ANO1 (HGNC:21625): (anoctamin 1) Enables calcium activated cation channel activity; intracellular calcium activated chloride channel activity; and iodide transmembrane transporter activity. Involved in cation transport; inorganic anion transport; and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in apical plasma membrane and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANO1 Gene-Disease associations (from GenCC):

• moyamoya disease 7

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intestinal dysmotility syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-0.251 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018043.7. 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
	ANO1	NM_018043.7	MANE Select	c.435C>T	p.Asp145Asp	synonymous	Exon 2 of 26	NP_060513.5
	ANO1	NM_001378092.1		c.558C>T	p.Asp186Asp	synonymous	Exon 3 of 28	NP_001365021.1	Q5XXA6-5
	ANO1	NM_001378093.1		c.435C>T	p.Asp145Asp	synonymous	Exon 3 of 26	NP_001365022.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO1	ENST00000355303.10	TSL:1 MANE Select	c.435C>T	p.Asp145Asp	synonymous	Exon 2 of 26	ENSP00000347454.5	Q5XXA6-1
	ANO1	ENST00000531349.6	TSL:1	c.558C>T	p.Asp186Asp	synonymous	Exon 3 of 28	ENSP00000432843.2	Q5XXA6-5
	ANO1	ENST00000930664.1		c.435C>T	p.Asp145Asp	synonymous	Exon 3 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes AF: 0.000371 AC: 46 AN: 123878 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000186

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000310

Gnomad OTH AF: 0.00311

GnomAD2 exomes AF: 0.000280 AC: 12 AN: 42844 AF XY: 0.000285

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000561

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000571

Gnomad NFE exome AF: 0.000108

Gnomad OTH exome AF: 0.00224

GnomAD4 exome AF: 0.0000673 AC: 82 AN: 1219232 Hom.: 0 Cov.: 34 AF XY: 0.0000529 AC XY: 31 AN XY: 586486

African (AFR) AF: 0.00 AC: 0 AN: 25614

American (AMR) AF: 0.00114 AC: 16 AN: 13984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17174

East Asian (EAS) AF: 0.00 AC: 0 AN: 29740

South Asian (SAS) AF: 0.00 AC: 0 AN: 46952

European-Finnish (FIN) AF: 0.000348 AC: 15 AN: 43044

Middle Eastern (MID) AF: 0.000405 AC: 2 AN: 4940

European-Non Finnish (NFE) AF: 0.0000344 AC: 34 AN: 987900

Other (OTH) AF: 0.000301 AC: 15 AN: 49884

GnomAD4 genome AF: 0.000371 AC: 46 AN: 123878 Hom.: 0 Cov.: 24 AF XY: 0.000402 AC XY: 23 AN XY: 57156

African (AFR) AF: 0.00 AC: 0 AN: 31068

American (AMR) AF: 0.00452 AC: 38 AN: 8404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4386

South Asian (SAS) AF: 0.00 AC: 0 AN: 4160

European-Finnish (FIN) AF: 0.000186 AC: 1 AN: 5368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 150

European-Non Finnish (NFE) AF: 0.0000310 AC: 2 AN: 64444

Other (OTH) AF: 0.00310 AC: 5 AN: 1614

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000574

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	10
DANN	Benign	0.94
PhyloP100		-0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs542259870; hg19: chr11-69934184;