12-49970924-G-A

Position:

• chr12-49970924-G-A

Variant summary

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

The ENST00000489786.5(AQP6):​n.1320+368G>A 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 0.463 in 151,968 control chromosomes in the GnomAD database, including 18,316 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 0.46 (18316 hom., cov: 32)
• Consequence: AQP6 ENST00000489786.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105369764	XR_001749143.2	n.208+4374C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP6	ENST00000489786.5	n.1320+368G>A		intron_variant, non_coding_transcript_variant		1
AQP6	ENST00000551733.5	c.-176+368G>A		intron_variant		3		ENSP00000449830

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70356 AN: 151850 Hom.: 18308 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.463 AC: 70371 AN: 151968 Hom.: 18316 Cov.: 32 AF XY: 0.463 AC XY: 34363 AN XY: 74268

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.483

Alfa AF: 0.570 Hom.: 34155

Bravo AF: 0.442

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1996315; hg19: chr12-50364707;