chr11-70078649-C-T

Variant names:

• chr11-70078649-C-T
• rs199763025
• NM_018043.7:c.43C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018043.7(ANO1):​c.43C>T​(p.Arg15Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000652 in 1,502,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: ANO1 NM_018043.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77
• Publications: 7 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]

LINC02584 (HGNC:33275): (long intergenic non-protein coding RNA 2584)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15349266).

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.43C>T	p.Arg15Cys	missense	Exon 1 of 26	NP_060513.5
	ANO1	NM_001378092.1		c.166C>T	p.Arg56Cys	missense	Exon 2 of 28	NP_001365021.1	Q5XXA6-5
	ANO1	NM_001378093.1		c.43C>T	p.Arg15Cys	missense	Exon 2 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.43C>T	p.Arg15Cys	missense	Exon 1 of 26	ENSP00000347454.5	Q5XXA6-1
	ANO1	ENST00000531349.6	TSL:1	c.166C>T	p.Arg56Cys	missense	Exon 2 of 28	ENSP00000432843.2	Q5XXA6-5
	ANO1	ENST00000930664.1		c.43C>T	p.Arg15Cys	missense	Exon 2 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes AF: 0.0000536 AC: 8 AN: 149298 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000105

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000498 AC: 10 AN: 200688 AF XY: 0.0000714

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000691

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000665 AC: 90 AN: 1352618 Hom.: 0 Cov.: 30 AF XY: 0.0000683 AC XY: 46 AN XY: 673200

African (AFR) AF: 0.000111 AC: 3 AN: 27140

American (AMR) AF: 0.0000797 AC: 3 AN: 37618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21910

East Asian (EAS) AF: 0.00 AC: 0 AN: 29002

South Asian (SAS) AF: 0.00 AC: 0 AN: 81254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48378

Middle Eastern (MID) AF: 0.000946 AC: 5 AN: 5286

European-Non Finnish (NFE) AF: 0.0000744 AC: 78 AN: 1048566

Other (OTH) AF: 0.0000187 AC: 1 AN: 53464

GnomAD4 genome AF: 0.0000535 AC: 8 AN: 149406 Hom.: 0 Cov.: 31 AF XY: 0.0000686 AC XY: 5 AN XY: 72878

African (AFR) AF: 0.0000242 AC: 1 AN: 41310

American (AMR) AF: 0.00 AC: 0 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000105 AC: 7 AN: 66954

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000239 AC: 2

ExAC AF: 0.0000584 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.095
Eigen_PC	Benign	-0.053
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.75	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.046	D
Polyphen		0.88	P
Vest4		0.19
MVP		0.54
MPC		0.91
ClinPred		0.12	T
GERP RS		2.2
PromoterAI		0.027	Neutral
Varity_R		0.14
gMVP		0.44
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs199763025; hg19: chr11-69924755; COSMIC: COSV62448061; COSMIC: COSV62448061;