dbSNP rs296766: AQP2:c.*1562T>C (chr12-49957170-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000486.6(AQP2):c.*1562T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,436 control chromosomes in the GnomAD database, including 65,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 65135 hom., cov: 33)

Exomes 𝑓: 0.97 ( 72 hom. )

Consequence

AQP2
NM_000486.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.86

Publications

15 publications found

Variant links:

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]

AQP2 links:

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

AQP5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-49957170-T-C is Benign according to our data. Variant chr12-49957170-T-C is described in ClinVar as Benign. ClinVar VariationId is 309255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000486.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP2	NM_000486.6	MANE Select	c.*1562T>C	3_prime_UTR	Exon 4 of 4	NP_000477.1	P41181
AQP5-AS1	NR_110590.1		n.257-2822A>G	intron	N/A
AQP5-AS1	NR_110591.1		n.118-5082A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP2	ENST00000199280.4	TSL:1 MANE Select	c.*1562T>C	3_prime_UTR	Exon 4 of 4	ENSP00000199280.3	P41181
AQP5-AS1	ENST00000550530.1	TSL:3	n.118-5082A>G	intron	N/A
AQP2	ENST00000551526.5	TSL:5	n.*115-318T>C	intron	N/A	ENSP00000447148.1	F8W0S2

Frequencies

GnomAD3 genomes

AF:

0.919

AC:

139868

AN:

152166

Hom.:

65085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.963

Gnomad ASJ

AF:

0.993

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.972

Gnomad FIN

AF:

0.965

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.995

Gnomad OTH

AF:

0.952

GnomAD4 exome

AF:

0.974

AC:

148

AN:

152

Hom.:

Cov.:

AF XY:

0.953

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.972

AC:

140

AN:

144

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.919

AC:

139973

AN:

152284

Hom.:

65135

Cov.:

AF XY:

0.919

AC XY:

68408

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.756

AC:

31407

AN:

41520

American (AMR)

AF:

0.963

AC:

14743

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.993

AC:

3447

AN:

3472

East Asian (EAS)

AF:

0.874

AC:

4522

AN:

5174

South Asian (SAS)

AF:

0.972

AC:

4692

AN:

4828

European-Finnish (FIN)

AF:

0.965

AC:

10248

AN:

10622

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.995

AC:

67700

AN:

68038

Other (OTH)

AF:

0.952

AC:

2013

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

500

1000

1501

2001

2501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.959

Hom.:

123808

Bravo

AF:

0.911

Asia WGS

AF:

0.911

AC:

3169

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Diabetes insipidus, nephrogenic, autosomal (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.34

(source)

DANN

Benign

0.50

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over