chr12-49951423-G-A

Position:

• chr12-49951423-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000486.6(AQP2):​c.360+233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 611,596 control chromosomes in the GnomAD database, including 66,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13797 hom., cov: 32)
  • Exomes 𝑓: 0.46 (52306 hom.)
• Consequence: AQP2 NM_000486.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.52

Genes affected

AQP2 (HGNC:634): (aquaporin 2) This gene encodes a water channel protein located in the kidney collecting tubule. It belongs to the MIP/aquaporin family, some members of which are clustered together on chromosome 12q13. Mutations in this gene have been linked to autosomal dominant and recessive forms of nephrogenic diabetes insipidus. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-49951423-G-A is Benign according to our data. Variant chr12-49951423-G-A is described in ClinVar as [Benign]. Clinvar id is 1276765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP2	NM_000486.6	c.360+233G>A		intron_variant		ENST00000199280.4	NP_000477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP2	ENST00000199280.4	c.360+233G>A		intron_variant		1	NM_000486.6	ENSP00000199280	P1
AQP2	ENST00000550862.1	c.360+233G>A		intron_variant		5		ENSP00000450022
AQP2	ENST00000551526.5	c.360+233G>A		intron_variant, NMD_transcript_variant		5		ENSP00000447148

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60686 AN: 151988 Hom.: 13789 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.460 AC: 211279 AN: 459490 Hom.: 52306 AF XY: 0.454 AC XY: 106397 AN XY: 234362

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.520

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.399 AC: 60706 AN: 152106 Hom.: 13797 Cov.: 32 AF XY: 0.397 AC XY: 29513 AN XY: 74364

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.414

Alfa AF: 0.474 Hom.: 4529

Bravo AF: 0.382

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.37
DANN	Benign	0.45

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: rs461872; hg19: chr12-50345206;