12-49974417-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001652.4(AQP6):c.496C>G(p.Arg166Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,613,756 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R166H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.014 ( 48 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 48 hom. )

Consequence

AQP6
NM_001652.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

AQP6 (HGNC:639): (aquaporin 6) The protein encoded by this gene is an aquaporin protein, which functions as a water channel in cells. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). This protein is specific for the kidney. This gene and related family members AQP0, AQP2, and AQP5 reside in a cluster on chromosome 12q13. [provided by RefSeq, Jul 2008]

AQP6 links:

LOC105369764 (HGNC:):

LOC105369764 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053281486).

BP6

Variant 12-49974417-C-G is Benign according to our data. Variant chr12-49974417-C-G is described in ClinVar as [Benign]. Clinvar id is 785405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2074/152308) while in subpopulation AFR AF= 0.0477 (1981/41552). AF 95% confidence interval is 0.0459. There are 48 homozygotes in gnomad4. There are 988 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP6	NM_001652.4 link	c.496C>G	p.Arg166Gly	missense_variant	Exon 2 of 4	ENST00000315520.10	NP_001643.2	Q13520
LOC105369764	XR_001749143.2 link	n.208+881G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AQP6	ENST00000315520.10 link	c.496C>G	p.Arg166Gly	missense_variant	Exon 2 of 4	1	NM_001652.4	ENSP00000320247.5	Q13520
AQP6	ENST00000489786.5 link	n.2915C>G		non_coding_transcript_exon_variant	Exon 5 of 7	1
AQP6	ENST00000551733 link	c.-27C>G		5_prime_UTR_variant	Exon 4 of 6	3		ENSP00000449830.1	F8VW87

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2070

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00815

GnomAD3 exomes

AF:

0.00366

AC:

919

AN:

250950

Hom.:

AF XY:

0.00272

AC XY:

369

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.0500

Gnomad AMR exome

AF:

0.00243

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:

0.000132

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00147

AC:

2155

AN:

1461448

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

931

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.0493

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.0136

AC:

2074

AN:

152308

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

988

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0477

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.000828

Hom.:

Bravo

AF:

0.0162

ESP6500AA

AF:

0.0470

AC:

207

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00470

AC:

571

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;D

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.96

.;D

MetaRNN

Benign

0.0053

T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.7

D;.

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.021

D;D

Polyphen

1.0

D;D

Vest4

0.29

MVP

0.97

MPC

0.80

ClinPred

0.056

GERP RS

3.4

Varity_R

0.73

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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