rs1399439

Positions:

• chr12-100827461-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO4	NM_001286615.2	c.-141+32434A>G		intron_variant		ENST00000392977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO4	ENST00000392977.8	c.-141+32434A>G		intron_variant		2	NM_001286615.2

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

Gnomad4 AFR AF: 0.00932

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.0309

Gnomad4 EAS AF: 0.0649

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0611

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0435 Hom.: 29

Bravo AF: 0.0328

Asia WGS AF: 0.0610 AC: 211 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs1399439; hg19: chr12-101221239;