12-101128300-C-G

Variant names:

• chr12-101128300-C-G
• rs1849710
• NM_001286615.2:c.*444C>G

Variant summary

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

The ENST00000392977.8(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 ENST00000392977.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 7 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392977.8. 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.*444C>G		3_prime_UTR	Exon 28 of 28	NP_001273544.1
	ANO4	NM_001286616.1		c.*448C>G		3_prime_UTR	Exon 27 of 27	NP_001273545.1
	ANO4	NM_178826.4		c.*444C>G		3_prime_UTR	Exon 27 of 27	NP_849148.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO4	ENST00000392977.8	TSL:2 MANE Select	c.*444C>G		3_prime_UTR	Exon 28 of 28	ENSP00000376703.3
	ANO4	ENST00000550015.1	TSL:2	n.1966C>G		non_coding_transcript_exon	Exon 15 of 15
	ANO4	ENST00000392979.7	TSL:2	c.*444C>G		3_prime_UTR	Exon 27 of 27	ENSP00000376705.3

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.110 AC: 47 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.101 AC: 4192 AN: 41516

American (AMR) AF: 0.131 AC: 1999 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3470

East Asian (EAS) AF: 0.187 AC: 965 AN: 5166

South Asian (SAS) AF: 0.184 AC: 886 AN: 4814

European-Finnish (FIN) AF: 0.105 AC: 1115 AN: 10590

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10152 AN: 67988

Other (OTH) AF: 0.146 AC: 308 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.8
DANN	Benign	0.64
PhyloP100		-0.037
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: rs1849710; hg19: chr12-101522078;