12-49970924-G-A

Variant names:

• chr12-49970924-G-A
• rs1996315
• ENST00000489786.5:n.1320+368G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000551733.5(AQP6):​c.-176+368G>A variant causes a intron 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 ENST00000551733.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 14 publications found

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]

AQP5-AS1 (HGNC:55474): (AQP5 and AQP2 antisense RNA 2)

LOC105369764 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551733.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP6	ENST00000489786.5	TSL:1	n.1320+368G>A		intron	N/A
	AQP6	ENST00000551733.5	TSL:3	c.-176+368G>A		intron	N/A	ENSP00000449830.1	F8VW87
	AQP5-AS1	ENST00000750790.1		n.178+3213C>T		intron	N/A

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

African (AFR) AF: 0.218 AC: 9017 AN: 41448

American (AMR) AF: 0.446 AC: 6816 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1642 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2166 AN: 5152

South Asian (SAS) AF: 0.598 AC: 2877 AN: 4810

European-Finnish (FIN) AF: 0.541 AC: 5711 AN: 10548

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40436 AN: 67948

Other (OTH) AF: 0.483 AC: 1019 AN: 2110

Alfa AF: 0.553 Hom.: 45257

Bravo AF: 0.442

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1996315; hg19: chr12-50364707;