12-100827461-A-G

Variant names:

• chr12-100827461-A-G
• rs1399439
• NM_001286615.2:c.-141+32434A>G

Variant summary

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

The NM_001286615.2(ANO4):​c.-141+32434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 152,070 control chromosomes in the GnomAD database, including 144 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 0.037 (144 hom., cov: 32)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 10 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0592 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO4	NM_001286615.2	MANE Select	c.-141+32434A>G		intron	N/A	NP_001273544.1
	ANO4	NM_178826.4		c.-141+32434A>G		intron	N/A	NP_849148.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO4	ENST00000392977.8	TSL:2 MANE Select	c.-141+32434A>G		intron	N/A	ENSP00000376703.3
	ANO4	ENST00000644049.1		c.359-74185A>G		intron	N/A	ENSP00000494481.1
	ANO4	ENST00000392979.7	TSL:2	c.-141+32434A>G		intron	N/A	ENSP00000376705.3

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5638 AN: 151952 Hom.: 144 Cov.: 32

Gnomad AFR AF: 0.00935

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.0647

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0371 AC: 5641 AN: 152070 Hom.: 144 Cov.: 32 AF XY: 0.0385 AC XY: 2865 AN XY: 74334

African (AFR) AF: 0.00932 AC: 387 AN: 41530

American (AMR) AF: 0.0261 AC: 398 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 107 AN: 3468

East Asian (EAS) AF: 0.0649 AC: 334 AN: 5148

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4828

European-Finnish (FIN) AF: 0.0611 AC: 647 AN: 10586

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0505 AC: 3427 AN: 67926

Other (OTH) AF: 0.0274 AC: 58 AN: 2114

Alfa AF: 0.0351 Hom.: 79

Bravo AF: 0.0328

Asia WGS AF: 0.0610 AC: 211 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.27
PhyloP100		-0.15
Mutation Taster		=100/0	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: rs1399439; hg19: chr12-101221239;