Genetic Variant AQP1:n.522G>C (chr7-30924207-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198098.4(AQP1):c.*578G>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 0.414 in 939,506 control chromosomes in the GnomAD database, including 86,219 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 23030 hom., cov: 33)

Exomes 𝑓: 0.39 ( 63189 hom. )

Consequence

AQP1
NM_198098.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.337

Publications

28 publications found

Variant links:

Genes affected

AQP1 (HGNC:633): (aquaporin 1 (Colton blood group)) This gene encodes a small integral membrane protein with six bilayer spanning domains that functions as a water channel protein. This protein permits passive transport of water along an osmotic gradient. This gene is a possible candidate for disorders involving imbalance in ocular fluid movement. [provided by RefSeq, Aug 2016]

AQP1 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

AQP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP1	NM_198098.4 link	c.*578G>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000311813.11	NP_932766.1	P29972-1A0A024RA31
AQP1	NM_001329872.2 link	c.*198G>C		3_prime_UTR_variant	Exon 5 of 5		NP_001316801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP1	ENST00000311813.11 link	c.*578G>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_198098.4	ENSP00000311165.4		P29972-1

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77983

AN:

152030

Hom.:

22981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.829

Gnomad AMI

AF:

0.536

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.404

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.496

GnomAD4 exome

AF:

0.395

AC:

310736

AN:

787358

Hom.:

63189

Cov.:

AF XY:

0.394

AC XY:

148346

AN XY:

376308

show subpopulations

African (AFR)

AF:

0.857

AC:

14284

AN:

16658

American (AMR)

AF:

0.430

AC:

3777

AN:

8786

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

3004

AN:

7566

East Asian (EAS)

AF:

0.348

AC:

3880

AN:

11146

South Asian (SAS)

AF:

0.423

AC:

14636

AN:

34566

European-Finnish (FIN)

AF:

0.332

AC:

2857

AN:

8612

Middle Eastern (MID)

AF:

0.455

AC:

795

AN:

1748

European-Non Finnish (NFE)

AF:

0.382

AC:

255801

AN:

669734

Other (OTH)

AF:

0.410

AC:

11702

AN:

28542

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8516

17032

25547

34063

42579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.513

AC:

78090

AN:

152148

Hom.:

23030

Cov.:

AF XY:

0.510

AC XY:

37915

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.830

AC:

34448

AN:

41510

American (AMR)

AF:

0.452

AC:

6906

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

1403

AN:

3472

East Asian (EAS)

AF:

0.381

AC:

1968

AN:

5162

South Asian (SAS)

AF:

0.421

AC:

2028

AN:

4820

European-Finnish (FIN)

AF:

0.340

AC:

3600

AN:

10586

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26043

AN:

67992

Other (OTH)

AF:

0.497

AC:

1049

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1703

3407

5110

6814

8517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.446

Hom.:

2320

Bravo

AF:

0.534

Asia WGS

AF:

0.458

AC:

1592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

(source)

DANN

Benign

0.75

PhyloP100

-0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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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7-30924207-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over