12-49972517-G-A

Position:

• chr12-49972517-G-A

Variant summary

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

The ENST00000551733.5(AQP6):​c.-139G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,254 control chromosomes in the GnomAD database, including 42,483 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 0.68 (42403 hom., cov: 31)
  • Exomes 𝑓: 0.88 (80 hom.)
• Consequence: AQP6 ENST00000551733.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

Genes affected

AQP6 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105369764	XR_001749143.2	n.208+2781C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP6	ENST00000489786.5	n.1357G>A		non_coding_transcript_exon_variant	4/7	1
AQP6	ENST00000551733.5	c.-139G>A		5_prime_UTR_variant	3/6	3		ENSP00000449830.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103690 AN: 151936 Hom.: 42402 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.884 AC: 175 AN: 198 Hom.: 80 Cov.: 0 AF XY: 0.871 AC XY: 101 AN XY: 116

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.903

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.682 AC: 103707 AN: 152056 Hom.: 42403 Cov.: 31 AF XY: 0.683 AC XY: 50750 AN XY: 74342

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.720

Alfa AF: 0.866 Hom.: 94741

Bravo AF: 0.643

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2849266; hg19: chr12-50366300;