rs1849710

chr12-101128300-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286615.2(ANO4):c.*444C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,592 control chromosomes in the GnomAD database, including 1,446 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 0.14 (1444 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2 hom.)
• Consequence: ANO4 NM_001286615.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO4	NM_001286615.2	c.*444C>G		3_prime_UTR_variant	28/28	ENST00000392977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO4	ENST00000392977.8	c.*444C>G		3_prime_UTR_variant	28/28	2	NM_001286615.2
ANO4	ENST00000392979.7	c.*444C>G		3_prime_UTR_variant	27/27	2		P1
ANO4	ENST00000550015.1	n.1966C>G		non_coding_transcript_exon_variant	15/15	2
ANO4	ENST00000644049.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20546 AN: 152040 Hom.: 1441 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.115 AC: 50 AN: 434 Hom.: 2 Cov.: 0 AF XY: 0.103 AC XY: 27 AN XY: 262

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.135 AC: 20557 AN: 152158 Hom.: 1444 Cov.: 32 AF XY: 0.133 AC XY: 9923 AN XY: 74360

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.146

Alfa AF: 0.129 Hom.: 178

Bravo AF: 0.136

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	2.8
Dann	Benign	0.64

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: rs1849710; hg19: chr12-101522078;