11-70078697-C-T

Variant names:

• chr11-70078697-C-T
• rs765946675
• NM_018043.7:c.91C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_018043.7(ANO1):​c.91C>T​(p.Leu31Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000471 in 1,486,662 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 0.000027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: ANO1 NM_018043.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=1.28 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.91C>T	p.Leu31Leu	synonymous	Exon 1 of 26	NP_060513.5
	ANO1	NM_001378092.1		c.214C>T	p.Leu72Leu	synonymous	Exon 2 of 28	NP_001365021.1	Q5XXA6-5
	ANO1	NM_001378093.1		c.91C>T	p.Leu31Leu	synonymous	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.91C>T	p.Leu31Leu	synonymous	Exon 1 of 26	ENSP00000347454.5	Q5XXA6-1
	ANO1	ENST00000531349.6	TSL:1	c.214C>T	p.Leu72Leu	synonymous	Exon 2 of 28	ENSP00000432843.2	Q5XXA6-5
	ANO1	ENST00000930664.1		c.91C>T	p.Leu31Leu	synonymous	Exon 2 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 149418 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000971

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000155 AC: 3 AN: 192996 AF XY: 0.00000923

Gnomad AFR exome AF: 0.000112

Gnomad AMR exome AF: 0.0000362

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000116

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000224 AC: 3 AN: 1337244 Hom.: 0 Cov.: 30 AF XY: 0.00000150 AC XY: 1 AN XY: 665672

African (AFR) AF: 0.0000376 AC: 1 AN: 26572

American (AMR) AF: 0.0000277 AC: 1 AN: 36102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21300

East Asian (EAS) AF: 0.00 AC: 0 AN: 27892

South Asian (SAS) AF: 0.00 AC: 0 AN: 79966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5220

European-Non Finnish (NFE) AF: 9.62e-7 AC: 1 AN: 1039980

Other (OTH) AF: 0.00 AC: 0 AN: 52418

GnomAD4 genome AF: 0.0000268 AC: 4 AN: 149418 Hom.: 0 Cov.: 31 AF XY: 0.0000274 AC XY: 2 AN XY: 72860

African (AFR) AF: 0.0000971 AC: 4 AN: 41202

American (AMR) AF: 0.00 AC: 0 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66994

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	0.98
PhyloP100		1.3
PromoterAI		0.16	Neutral

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: rs765946675; hg19: chr11-69924803;