rs10507120

chr12-100856482-C-Achr12-100856482-C-Gchr12-100856482-C-T

Variant summary

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

The NM_001286615.2(ANO4):c.-140-45164C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,904 control chromosomes in the GnomAD database, including 12,091 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 0.40 (12091 hom., cov: 32)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO4	NM_001286615.2	c.-140-45164C>A		intron_variant		ENST00000392977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO4	ENST00000392977.8	c.-140-45164C>A		intron_variant		2	NM_001286615.2
	ENST00000552332.1	n.198+2583G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59972 AN: 151786 Hom.: 12075 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.395 AC: 60030 AN: 151904 Hom.: 12091 Cov.: 32 AF XY: 0.392 AC XY: 29128 AN XY: 74218

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.390

Alfa AF: 0.297 Hom.: 1059

Bravo AF: 0.411

Asia WGS AF: 0.395 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.6
Dann	Benign	0.56

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: rs10507120; hg19: chr12-101250260;