Genetic Variant AQP12A:c.124-15C>G (chr2-240692059-C-G) – 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_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

Publications

10 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198998.3. 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
	AQP12A	NM_198998.3	MANE Select	c.124-15C>G		intron	N/A	NP_945349.1	Q8IXF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP12A	ENST00000337801.9	TSL:1 MANE Select	c.124-15C>G		intron	N/A	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

GnomAD2 exomes

AF:

0.545

AC:

128231

AN:

235192

AF XY:

0.535

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 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

African (AFR)

AF:

0.722

AC:

22661

AN:

31380

American (AMR)

AF:

0.660

AC:

24894

AN:

37732

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

15617

AN:

25644

East Asian (EAS)

AF:

0.481

AC:

17879

AN:

37204

South Asian (SAS)

AF:

0.455

AC:

37813

AN:

83038

European-Finnish (FIN)

AF:

0.489

AC:

25615

AN:

52422

Middle Eastern (MID)

AF:

0.616

AC:

3261

AN:

5296

European-Non Finnish (NFE)

AF:

0.529

AC:

582021

AN:

1099314

Other (OTH)

AF:

0.549

AC:

32368

AN:

58922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

23601

47202

70802

94403

118004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15642

31284

46926

62568

78210

<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:

0.590

AC:

84066

AN:

142462

Hom.:

29212

Cov.:

AF XY:

0.588

AC XY:

40764

AN XY:

69328

show subpopulations

African (AFR)

AF:

0.727

AC:

26606

AN:

36594

American (AMR)

AF:

0.627

AC:

8405

AN:

13410

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

2116

AN:

3324

East Asian (EAS)

AF:

0.526

AC:

2424

AN:

4608

South Asian (SAS)

AF:

0.462

AC:

2092

AN:

4528

European-Finnish (FIN)

AF:

0.491

AC:

5019

AN:

10228

Middle Eastern (MID)

AF:

0.589

AC:

165

AN:

280

European-Non Finnish (NFE)

AF:

0.533

AC:

35491

AN:

66636

Other (OTH)

AF:

0.594

AC:

1166

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1339

2677

4016

5354

6693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.568

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.021

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

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

PhyloP100

0.34

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

PromoterAI

0.016

Neutral

(source)

gMVP

0.43

Mutation Taster

=99/1

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