12-49953905-T-G

Variant names:

• chr12-49953905-T-G
• rs61926092
• NM_000486.6:c.361-250T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000486.6(AQP2):​c.361-250T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,964 control chromosomes in the GnomAD database, including 3,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3047 hom., cov: 32)
• Consequence: AQP2 NM_000486.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.964

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]

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-49953905-T-G is Benign according to our data. Variant chr12-49953905-T-G is described in ClinVar as [Benign]. Clinvar id is 1253315.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP2	NM_000486.6	c.361-250T>G		intron_variant	Intron 1 of 3	ENST00000199280.4	NP_000477.1
AQP5-AS1	NR_110590.1	n.471+229A>C		intron_variant	Intron 2 of 2
AQP5-AS1	NR_110591.1	n.118-1817A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP2	ENST00000199280.4	c.361-250T>G		intron_variant	Intron 1 of 3	1	NM_000486.6	ENSP00000199280.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28968 AN: 151846 Hom.: 3047 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.191 AC: 28974 AN: 151964 Hom.: 3047 Cov.: 32 AF XY: 0.192 AC XY: 14297 AN XY: 74274

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.220

Alfa AF: 0.109 Hom.: 207

Bravo AF: 0.183

Asia WGS AF: 0.250 AC: 867 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.085
DANN	Benign	0.62

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: rs61926092; hg19: chr12-50347688;