rs2056075

Variant names:

• chr12-100856097-A-G
• rs2056075
• NM_001286615.2:c.-140-45549A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-100856097-A-G
• chr12-100856097-A-T

Variant summary

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

The NM_001286615.2(ANO4):​c.-140-45549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,934 control chromosomes in the GnomAD database, including 12,675 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 0.41 (12675 hom., cov: 32)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO4	NM_001286615.2	c.-140-45549A>G		intron_variant	Intron 1 of 27	ENST00000392977.8	NP_001273544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO4	ENST00000392977.8	c.-140-45549A>G		intron_variant	Intron 1 of 27	2	NM_001286615.2	ENSP00000376703.3

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61510 AN: 151816 Hom.: 12660 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.405 AC: 61567 AN: 151934 Hom.: 12675 Cov.: 32 AF XY: 0.403 AC XY: 29903 AN XY: 74254

African (AFR) AF: 0.431 AC: 17862 AN: 41416

American (AMR) AF: 0.478 AC: 7283 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2346 AN: 5150

South Asian (SAS) AF: 0.334 AC: 1612 AN: 4828

European-Finnish (FIN) AF: 0.325 AC: 3432 AN: 10566

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26759 AN: 67936

Other (OTH) AF: 0.399 AC: 845 AN: 2116

Alfa AF: 0.401 Hom.: 16247

Bravo AF: 0.420

Asia WGS AF: 0.400 AC: 1393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		0.45
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: rs2056075; hg19: chr12-101249875;