rs371777

Variant names:

• chr12-49955340-C-A
• rs371777
• NM_000486.6:c.607-59C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-49955340-C-A
• chr12-49955340-C-T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.935
• Publications: 7 publications found

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)

ENSG00000257378 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
AQP2	NM_000486.6	c.607-59C>A		intron_variant	Intron 3 of 3	ENST00000199280.4	NP_000477.1
AQP5-AS1	NR_110590.1	n.257-992G>T		intron_variant	Intron 1 of 2
AQP5-AS1	NR_110591.1	n.118-3252G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP2	ENST00000199280.4	c.607-59C>A		intron_variant	Intron 3 of 3	1	NM_000486.6	ENSP00000199280.3

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

African (AFR) AF: 0.436 AC: 13872 AN: 31804

American (AMR) AF: 0.772 AC: 32181 AN: 41672

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 12335 AN: 24596

East Asian (EAS) AF: 0.606 AC: 23147 AN: 38198

South Asian (SAS) AF: 0.637 AC: 52529 AN: 82466

European-Finnish (FIN) AF: 0.696 AC: 34924 AN: 50148

Middle Eastern (MID) AF: 0.518 AC: 2418 AN: 4672

European-Non Finnish (NFE) AF: 0.615 AC: 658945 AN: 1072130

Other (OTH) AF: 0.592 AC: 34224 AN: 57846

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

African (AFR) AF: 0.443 AC: 18373 AN: 41518

American (AMR) AF: 0.689 AC: 10529 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3472

East Asian (EAS) AF: 0.621 AC: 3200 AN: 5154

South Asian (SAS) AF: 0.626 AC: 3020 AN: 4828

European-Finnish (FIN) AF: 0.697 AC: 7382 AN: 10592

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42096 AN: 67986

Other (OTH) AF: 0.579 AC: 1223 AN: 2114

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diabetes insipidus, nephrogenic, autosomal Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.79
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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