rs1849929

Positions:

• chr12-101067143-A-T

Variant summary

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

The NM_001286615.2(ANO4):​c.1313-12050A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 313,748 control chromosomes in the GnomAD database, including 10,096 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 0.20 (3927 hom., cov: 32)
  • Exomes 𝑓: 0.26 (6169 hom.)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722

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]

SNX5P2 (HGNC:41513): (sorting nexin 5 pseudogene 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO4	NM_001286615.2	c.1313-12050A>T		intron_variant		ENST00000392977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO4	ENST00000392977.8	c.1313-12050A>T		intron_variant		2	NM_001286615.2
SNX5P2	ENST00000547000.1	n.311+99A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30337 AN: 151980 Hom.: 3931 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.256 AC: 41352 AN: 161650 Hom.: 6169 AF XY: 0.264 AC XY: 22926 AN XY: 86906

Gnomad4 AFR exome AF: 0.0488

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.532

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.199 AC: 30325 AN: 152098 Hom.: 3927 Cov.: 32 AF XY: 0.208 AC XY: 15426 AN XY: 74334

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.223

Alfa AF: 0.204 Hom.: 501

Bravo AF: 0.190

Asia WGS AF: 0.408 AC: 1413 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.49

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: rs1849929; hg19: chr12-101460921;