rs371777

chr12-49955340-C-Achr12-49955340-C-T

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.607-59C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,555,686 control chromosomes in the GnomAD database, including 294,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26327 hom., cov: 34)
  • Exomes 𝑓: 0.62 (267900 hom.)
• Consequence: AQP2 NM_000486.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.935

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)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-49955340-C-A is Benign according to our data. Variant chr12-49955340-C-A is described in ClinVar as [Benign]. Clinvar id is 1180565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP2	NM_000486.6	c.607-59C>A		intron_variant		ENST00000199280.4
AQP5-AS1	NR_110591.1	n.118-3252G>T		intron_variant, non_coding_transcript_variant
AQP5-AS1	NR_110590.1	n.257-992G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP2	ENST00000199280.4	c.607-59C>A		intron_variant		1	NM_000486.6	P1
AQP5-AS1	ENST00000550530.1	n.118-3252G>T		intron_variant, non_coding_transcript_variant		3
	ENST00000552806.1	n.541+245G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88156 AN: 152036 Hom.: 26295 Cov.: 34

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.616 AC: 864575 AN: 1403532 Hom.: 267900 AF XY: 0.617 AC XY: 429159 AN XY: 695922

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.606

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.696

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.580 AC: 88233 AN: 152154 Hom.: 26327 Cov.: 34 AF XY: 0.585 AC XY: 43498 AN XY: 74382

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.579

Alfa AF: 0.527 Hom.: 1774

Bravo AF: 0.575

Asia WGS AF: 0.640 AC: 2226 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Diabetes insipidus, nephrogenic, autosomal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.0
Dann	Benign	0.79

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: rs371777; hg19: chr12-50349123; COSMIC: COSV52230541; COSMIC: COSV52230541;