chr12-100744118-A-G

Position:

• chr12-100744118-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	Protein	UniProt
ANO4	XM_011537911.3	c.451+4013A>G		intron_variant			XP_011536213.2
ANO4	XM_011537912.3	c.451+4013A>G		intron_variant			XP_011536214.2
ANO4	XM_011537913.3	c.451+4013A>G		intron_variant			XP_011536215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO4	ENST00000644049.1	c.358+4013A>G		intron_variant				ENSP00000494481
ANO4	ENST00000549155.6	c.358+4013A>G		intron_variant, NMD_transcript_variant		2		ENSP00000449116

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

Gnomad4 AFR AF: 0.0669

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.0863

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.170

Alfa AF: 0.102 Hom.: 207

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10507117; hg19: chr12-101137896;