rs296763

chr12-49969231-G-C

Variant summary

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

The ENST00000489786.5(AQP6):n.1138+234G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,176 control chromosomes in the GnomAD database, including 3,933 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 0.22 (3933 hom., cov: 33)
• Consequence: AQP6 ENST00000489786.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

Genes affected

AQP6 (HGNC:639): (aquaporin 6) The protein encoded by this gene is an aquaporin protein, which functions as a water channel in cells. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). This protein is specific for the kidney. This gene and related family members AQP0, AQP2, and AQP5 reside in a cluster on chromosome 12q13. [provided by RefSeq, Jul 2008]

LOC105369764 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105369764	XR_001749143.2	n.209-3426C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP6	ENST00000489786.5	n.1138+234G>C		intron_variant, non_coding_transcript_variant		1
AQP6	ENST00000551733.5	c.-357-1144G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33325 AN: 152058 Hom.: 3933 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0778

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.219 AC: 33337 AN: 152176 Hom.: 3933 Cov.: 33 AF XY: 0.217 AC XY: 16177 AN XY: 74390

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.00984

Gnomad4 SAS AF: 0.0781

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.217

Alfa AF: 0.234 Hom.: 577

Bravo AF: 0.214

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.5
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs296763; hg19: chr12-50363014;