12-49955982-C-T

Variant names:

• chr12-49955982-C-T
• rs467323
• NM_000486.6:c.*374C>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.*374C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 424,518 control chromosomes in the GnomAD database, including 79,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (25039 hom., cov: 32)
  • Exomes 𝑓: 0.61 (54437 hom.)
• Consequence: AQP2 NM_000486.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.521
• Publications: 17 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]

ENSG00000257378 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-49955982-C-T is Benign according to our data. Variant chr12-49955982-C-T is described in ClinVar as Benign. ClinVar VariationId is 309241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP2	NM_000486.6	MANE Select	c.*374C>T		3_prime_UTR	Exon 4 of 4	NP_000477.1
	AQP5-AS1	NR_110590.1		n.257-1634G>A		intron	N/A
	AQP5-AS1	NR_110591.1		n.118-3894G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP2	ENST00000199280.4	TSL:1 MANE Select	c.*374C>T		3_prime_UTR	Exon 4 of 4	ENSP00000199280.3
	ENSG00000257378	ENST00000552806.1	TSL:5	n.144G>A		non_coding_transcript_exon	Exon 1 of 2
	AQP5-AS1	ENST00000550530.1	TSL:3	n.118-3894G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79899 AN: 151986 Hom.: 25033 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.605 AC: 164843 AN: 272416 Hom.: 54437 Cov.: 0 AF XY: 0.586 AC XY: 83288 AN XY: 142038

African (AFR) AF: 0.202 AC: 1715 AN: 8506

American (AMR) AF: 0.516 AC: 6138 AN: 11894

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 5107 AN: 8282

East Asian (EAS) AF: 0.233 AC: 3830 AN: 16458

South Asian (SAS) AF: 0.337 AC: 11471 AN: 34020

European-Finnish (FIN) AF: 0.722 AC: 10711 AN: 14840

Middle Eastern (MID) AF: 0.563 AC: 1197 AN: 2126

European-Non Finnish (NFE) AF: 0.717 AC: 114932 AN: 160286

Other (OTH) AF: 0.609 AC: 9742 AN: 16004

GnomAD4 genome AF: 0.526 AC: 79932 AN: 152102 Hom.: 25039 Cov.: 32 AF XY: 0.521 AC XY: 38764 AN XY: 74384

African (AFR) AF: 0.207 AC: 8599 AN: 41484

American (AMR) AF: 0.536 AC: 8187 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1215 AN: 5158

South Asian (SAS) AF: 0.324 AC: 1560 AN: 4820

European-Finnish (FIN) AF: 0.702 AC: 7446 AN: 10608

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48838 AN: 67968

Other (OTH) AF: 0.552 AC: 1163 AN: 2108

Alfa AF: 0.667 Hom.: 38897

Bravo AF: 0.504

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Diabetes insipidus, nephrogenic, autosomal (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.51
PhyloP100		0.52
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: rs467323; hg19: chr12-50349765;