12-100744118-A-G

Variant names:

• chr12-100744118-A-G
• rs10507117
• ENST00000644049.1:c.358+4013A>G

Variant summary

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

The ENST00000644049.1(ANO4):​c.358+4013A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,188 control chromosomes in the GnomAD database, including 2,074 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 (2074 hom., cov: 32)
• Consequence: ANO4 ENST00000644049.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO4	XM_011537911.3	c.451+4013A>G		intron_variant	Intron 3 of 29		XP_011536213.2
ANO4	XM_011537912.3	c.451+4013A>G		intron_variant	Intron 3 of 29		XP_011536214.2
ANO4	XM_011537913.3	c.451+4013A>G		intron_variant	Intron 3 of 28		XP_011536215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO4	ENST00000644049.1	c.358+4013A>G		intron_variant	Intron 3 of 29			ENSP00000494481.1
ANO4	ENST00000549155.6	n.358+4013A>G		intron_variant	Intron 3 of 10	2		ENSP00000449116.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22002 AN: 152070 Hom.: 2066 Cov.: 32

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.145 AC: 22014 AN: 152188 Hom.: 2074 Cov.: 32 AF XY: 0.148 AC XY: 10996 AN XY: 74390

African (AFR) AF: 0.0669 AC: 2777 AN: 41530

American (AMR) AF: 0.289 AC: 4415 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1423 AN: 5174

South Asian (SAS) AF: 0.261 AC: 1257 AN: 4824

European-Finnish (FIN) AF: 0.0863 AC: 914 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10212 AN: 68006

Other (OTH) AF: 0.170 AC: 360 AN: 2112

Alfa AF: 0.101 Hom.: 208

Bravo AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10507117; hg19: chr12-101137896;