7-30912043-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_198098.4(AQP1):c.134C>T(p.Ala45Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,613,408 control chromosomes in the GnomAD database, including 1,258 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 83 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1175 hom. )

Consequence

AQP1
NM_198098.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.654

Publications

29 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:

ENSG00000250424 (HGNC:):

ENSG00000250424 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002882719).

BP6

Variant 7-30912043-C-T is Benign according to our data. Variant chr7-30912043-C-T is described in ClinVar as Benign. ClinVar VariationId is 17846.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0269 (4100/152294) while in subpopulation NFE AF = 0.0419 (2848/68018). AF 95% confidence interval is 0.0406. There are 83 homozygotes in GnomAd4. There are 1940 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP1	NM_198098.4 link	c.134C>T	p.Ala45Val	missense_variant	Exon 1 of 4	ENST00000311813.11	NP_932766.1	P29972-1A0A024RA31
AQP1	NM_001329872.2 link	c.134C>T	p.Ala45Val	missense_variant	Exon 1 of 5		NP_001316801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP1	ENST00000311813.11 link	c.134C>T	p.Ala45Val	missense_variant	Exon 1 of 4	1	NM_198098.4	ENSP00000311165.4		P29972-1
ENSG00000250424	ENST00000509504.2 link	c.671C>T	p.Ala224Val	missense_variant	Exon 8 of 11	5		ENSP00000421315.2		K7N7A8

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4103

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0423

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0419

Gnomad OTH

AF:

0.0205

GnomAD2 exomes

AF:

0.0260

AC:

6529

AN:

251044

AF XY:

0.0265

show subpopulations

Gnomad AFR exome

AF:

0.00808

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.00923

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0380

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0251

GnomAD4 exome

AF:

0.0372

AC:

54398

AN:

1461114

Hom.:

1175

Cov.:

AF XY:

0.0363

AC XY:

26418

AN XY:

726874

show subpopulations

African (AFR)

AF:

0.00774

AC:

259

AN:

33480

American (AMR)

AF:

0.0110

AC:

491

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00999

AC:

261

AN:

26136

East Asian (EAS)

AF:

0.00141

AC:

AN:

39700

South Asian (SAS)

AF:

0.00537

AC:

463

AN:

86258

European-Finnish (FIN)

AF:

0.0386

AC:

2035

AN:

52680

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0440

AC:

48923

AN:

1111988

Other (OTH)

AF:

0.0310

AC:

1873

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

3720

7439

11159

14878

18598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1788

3576

5364

7152

8940

<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:

0.0269

AC:

4100

AN:

152294

Hom.:

Cov.:

AF XY:

0.0261

AC XY:

1940

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0101

AC:

418

AN:

41578

American (AMR)

AF:

0.0144

AC:

220

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

AN:

3472

East Asian (EAS)

AF:

0.000773

AC:

AN:

5176

South Asian (SAS)

AF:

0.00456

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0423

AC:

449

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0419

AC:

2848

AN:

68018

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

203

405

608

810

1013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0317

Hom.:

226

Bravo

AF:

0.0239

TwinsUK

AF:

0.0475

AC:

176

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.0409

AC:

352

ExAC

AF:

0.0263

AC:

3198

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0391

EpiControl

AF:

0.0366

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

COLTON BLOOD GROUP POLYMORPHISM

Benign:1

Sep 01, 1994

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.48

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.86

PhyloP100

0.65

PROVEAN

Benign

-0.45

REVEL

Benign

0.17

Sift

Benign

0.15

Sift4G

Benign

0.44

Polyphen

0.0070

Vest4

0.059

MPC

0.41

ClinPred

0.0044

GERP RS

0.58

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.61

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over