Genetic Variant AQP12A:c.124-15C>G (chr2-240692059-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198998.3(AQP12A):c.124-15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,573,414 control chromosomes in the GnomAD database, including 269,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 29212 hom., cov: 29)

Exomes 𝑓: 0.53 ( 240757 hom. )

Consequence

AQP12A
NM_198998.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.345

Variant links:

Genes affected

AQP12A (HGNC:19941): (aquaporin 12A) Predicted to enable channel activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AQP12A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.851267E-6).

BP6

Variant 2-240692059-C-G is Benign according to our data. Variant chr2-240692059-C-G is described in ClinVar as [Benign]. Clinvar id is 1247827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP12A	NM_198998.3 link	c.124-15C>G		intron_variant	Intron 1 of 3	ENST00000337801.9	NP_945349.1	Q8IXF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP12A	ENST00000337801.9 link	c.124-15C>G		intron_variant	Intron 1 of 3	1	NM_198998.3	ENSP00000337144.4		Q8IXF9

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

84000

AN:

142380

Hom.:

29176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.727

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.603

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.603

GnomAD3 exomes

AF:

0.545

AC:

128231

AN:

235192

Hom.:

42721

AF XY:

0.535

AC XY:

68770

AN XY:

128450

show subpopulations

Gnomad AFR exome

AF:

0.711

Gnomad AMR exome

AF:

0.658

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.534

Gnomad SAS exome

AF:

0.442

Gnomad FIN exome

AF:

0.478

Gnomad NFE exome

AF:

0.530

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.533

AC:

762129

AN:

1430952

Hom.:

240757

Cov.:

129

AF XY:

0.529

AC XY:

376897

AN XY:

712186

show subpopulations

Gnomad4 AFR exome

AF:

0.722

Gnomad4 AMR exome

AF:

0.660

Gnomad4 ASJ exome

AF:

0.609

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.455

Gnomad4 FIN exome

AF:

0.489

Gnomad4 NFE exome

AF:

0.529

Gnomad4 OTH exome

AF:

0.549

GnomAD4 genome

AF:

0.590

AC:

84066

AN:

142462

Hom.:

29212

Cov.:

AF XY:

0.588

AC XY:

40764

AN XY:

69328

show subpopulations

Gnomad4 AFR

AF:

0.727

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.637

Gnomad4 EAS

AF:

0.526

Gnomad4 SAS

AF:

0.462

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.594

Alfa

AF:

0.568

Hom.:

4798

ESP6500AA

AF:

0.703

AC:

2914

ESP6500EA

AF:

0.531

AC:

4516

ExAC

AF:

0.536

AC:

62803

Asia WGS

AF:

0.444

AC:

1482

AN:

3326

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.52

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0000019

MetaSVM

Benign

-1.0

PROVEAN

Benign

3.6

REVEL

Benign

0.047

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.020

ClinPred

0.0019

GERP RS

2.4

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over