chr12-100856482-C-A

Variant names:

• chr12-100856482-C-A
• rs10507120
• NM_001286615.2:c.-140-45164C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286615.2(ANO4):​c.-140-45164C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,904 control chromosomes in the GnomAD database, including 12,091 homozygotes. 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 0.40 (12091 hom., cov: 32)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 3 publications found

Genes affected

ANO4 (HGNC:23837): (anoctamin 4) Enables intracellular calcium activated chloride channel activity. Involved in chloride transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ANO4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000257325 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286615.2. 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
	ANO4	NM_001286615.2	MANE Select	c.-140-45164C>A		intron	N/A	NP_001273544.1	Q32M45-1
	ANO4	NM_178826.4		c.-140-45164C>A		intron	N/A	NP_849148.2	Q32M45-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO4	ENST00000392977.8	TSL:2 MANE Select	c.-140-45164C>A		intron	N/A	ENSP00000376703.3	Q32M45-1
	ANO4	ENST00000644049.1		c.359-45164C>A		intron	N/A	ENSP00000494481.1	A0A2R8Y532
	ANO4	ENST00000852684.1		c.-140-45164C>A		intron	N/A	ENSP00000522743.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59972 AN: 151786 Hom.: 12075 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.390

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.395 AC: 60030 AN: 151904 Hom.: 12091 Cov.: 32 AF XY: 0.392 AC XY: 29128 AN XY: 74218

African (AFR) AF: 0.428 AC: 17710 AN: 41416

American (AMR) AF: 0.469 AC: 7152 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2329 AN: 5130

South Asian (SAS) AF: 0.327 AC: 1579 AN: 4824

European-Finnish (FIN) AF: 0.311 AC: 3275 AN: 10546

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25753 AN: 67948

Other (OTH) AF: 0.390 AC: 823 AN: 2108

Alfa AF: 0.303 Hom.: 1129

Bravo AF: 0.411

Asia WGS AF: 0.395 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

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: rs10507120; hg19: chr12-101250260;