7-30912228-G-A

Position:

chr7-30912228-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_198098.4(AQP1):c.319G>A(p.Val107Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00225 in 1,609,482 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 44 hom. )

Consequence

AQP1
NM_198098.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.79

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009975493).

BP6

Variant 7-30912228-G-A is Benign according to our data. Variant chr7-30912228-G-A is described in ClinVar as [Benign]. Clinvar id is 1593419.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00233 (3398/1457166) while in subpopulation SAS AF= 0.0197 (1700/86258). AF 95% confidence interval is 0.0189. There are 44 homozygotes in gnomad4_exome. There are 2114 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP1	NM_198098.4 linkuse as main transcript	c.319G>A	p.Val107Ile	missense_variant	1/4	ENST00000311813.11	NP_932766.1
AQP1	NM_001329872.2 linkuse as main transcript	c.319G>A	p.Val107Ile	missense_variant	1/5		NP_001316801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP1	ENST00000311813.11 linkuse as main transcript	c.319G>A	p.Val107Ile	missense_variant	1/4	1	NM_198098.4	ENSP00000311165	P1	P29972-1
AQP1	ENST00000441328.7 linkuse as main transcript	n.174G>A		non_coding_transcript_exon_variant	1/2	1
AQP1	ENST00000652696.1 linkuse as main transcript	c.319G>A	p.Val107Ile	missense_variant	1/5			ENSP00000498672	P1	P29972-1
AQP1	ENST00000652692.1 linkuse as main transcript	c.109G>A	p.Val37Ile	missense_variant	1/5			ENSP00000498806

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

219

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00360

AC:

890

AN:

247352

Hom.:

AF XY:

0.00459

AC XY:

615

AN XY:

134092

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.000869

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.0214

Gnomad FIN exome

AF:

0.0000540

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.00233

AC:

3398

AN:

1457166

Hom.:

Cov.:

AF XY:

0.00292

AC XY:

2114

AN XY:

725148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00360

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0197

Gnomad4 FIN exome

AF:

0.0000615

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.00144

AC:

219

AN:

152316

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.00106

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00372

AC:

452

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AQP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.010

MetaSVM

Uncertain

-0.047

MutationAssessor

Benign

0.92

MutationTaster

Benign

0.99

D;D

PROVEAN

Benign

-0.65

REVEL

Uncertain

0.38

Sift

Benign

0.40

Sift4G

Benign

0.51

Polyphen

1.0

Vest4

0.36

MVP

0.79

MPC

1.1

ClinPred

0.023

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.66

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