11-70078642-C-T

Variant names:

• chr11-70078642-C-T
• rs746101530
• NM_018043.7:c.36C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018043.7(ANO1):​c.36C>T​(p.Ala12Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,352,438 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. Synonymous variant affecting the same amino acid position (i.e. A12A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ANO1 NM_018043.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.691
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.691 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.36C>T	p.Ala12Ala	synonymous	Exon 1 of 26	NP_060513.5
	ANO1	NM_001378092.1		c.159C>T	p.Ala53Ala	synonymous	Exon 2 of 28	NP_001365021.1	Q5XXA6-5
	ANO1	NM_001378093.1		c.36C>T	p.Ala12Ala	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.36C>T	p.Ala12Ala	synonymous	Exon 1 of 26	ENSP00000347454.5	Q5XXA6-1
	ANO1	ENST00000531349.6	TSL:1	c.159C>T	p.Ala53Ala	synonymous	Exon 2 of 28	ENSP00000432843.2	Q5XXA6-5
	ANO1	ENST00000930664.1		c.36C>T	p.Ala12Ala	synonymous	Exon 2 of 26	ENSP00000600723.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1352438 Hom.: 0 Cov.: 30 AF XY: 0.00000149 AC XY: 1 AN XY: 673112

African (AFR) AF: 0.00 AC: 0 AN: 27118

American (AMR) AF: 0.00 AC: 0 AN: 37470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21918

East Asian (EAS) AF: 0.00 AC: 0 AN: 28880

South Asian (SAS) AF: 0.00 AC: 0 AN: 81144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5292

European-Non Finnish (NFE) AF: 9.54e-7 AC: 1 AN: 1048758

Other (OTH) AF: 0.00 AC: 0 AN: 53446

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		0.69
PromoterAI		-0.035	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: rs746101530; hg19: chr11-69924748;