NM_001286615.2:c.-140-34966A>G

Variant names:

• chr12-100866680-A-G
• rs938335
• NM_001286615.2:c.-140-34966A>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.-140-34966A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 151,900 control chromosomes in the GnomAD database, including 35,625 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 0.68 (35625 hom., cov: 31)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO4	NM_001286615.2	c.-140-34966A>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.-140-34966A>G		intron_variant	Intron 1 of 27	2	NM_001286615.2	ENSP00000376703.3

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103860 AN: 151782 Hom.: 35611 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.684 AC: 103927 AN: 151900 Hom.: 35625 Cov.: 31 AF XY: 0.683 AC XY: 50684 AN XY: 74234

African (AFR) AF: 0.674 AC: 27912 AN: 41408

American (AMR) AF: 0.729 AC: 11118 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2477 AN: 3470

East Asian (EAS) AF: 0.680 AC: 3495 AN: 5136

South Asian (SAS) AF: 0.629 AC: 3029 AN: 4816

European-Finnish (FIN) AF: 0.674 AC: 7107 AN: 10548

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46573 AN: 67950

Other (OTH) AF: 0.686 AC: 1447 AN: 2110

Alfa AF: 0.686 Hom.: 103652

Bravo AF: 0.690

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.78
PhyloP100		-0.81
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: rs938335; hg19: chr12-101260458;