7-30912192-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000311813.11(AQP1):​c.283C>T​(p.Leu95Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

AQP1
ENST00000311813.11 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11788118).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AQP1NM_198098.4 linkuse as main transcriptc.283C>T p.Leu95Phe missense_variant 1/4 ENST00000311813.11 NP_932766.1
AQP1NM_001329872.2 linkuse as main transcriptc.283C>T p.Leu95Phe missense_variant 1/5 NP_001316801.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AQP1ENST00000311813.11 linkuse as main transcriptc.283C>T p.Leu95Phe missense_variant 1/41 NM_198098.4 ENSP00000311165 P1P29972-1
AQP1ENST00000441328.7 linkuse as main transcriptn.138C>T non_coding_transcript_exon_variant 1/21
AQP1ENST00000652696.1 linkuse as main transcriptc.283C>T p.Leu95Phe missense_variant 1/5 ENSP00000498672 P1P29972-1
AQP1ENST00000652692.1 linkuse as main transcriptc.73C>T p.Leu25Phe missense_variant 1/5 ENSP00000498806

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250054
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135342
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460114
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726458
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152222
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 10, 2022The c.283C>T (p.L95F) alteration is located in exon 1 (coding exon 1) of the AQP1 gene. This alteration results from a C to T substitution at nucleotide position 283, causing the leucine (L) at amino acid position 95 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
1.0
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.54
D
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
1.0
N;N
PROVEAN
Benign
-0.87
N
REVEL
Uncertain
0.32
Sift
Benign
0.34
T
Sift4G
Benign
0.27
T
Polyphen
0.31
B
Vest4
0.12
MVP
0.68
MPC
0.43
ClinPred
0.20
T
GERP RS
-4.6
Varity_R
0.18
gMVP
0.77

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.

Other links and lift over

dbSNP: rs372063183; hg19: chr7-30951807; API