Variant 12-49973230-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001652.4(AQP6):c.57T>C(p.Leu19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,613,884 control chromosomes in the GnomAD database, including 282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 145 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 137 hom. )

Consequence

AQP6
NM_001652.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.156

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 12-49973230-T-C is Benign according to our data. Variant chr12-49973230-T-C is described in ClinVar as [Benign]. Clinvar id is 785404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.156 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP6	NM_001652.4 linkuse as main transcript	c.57T>C	p.Leu19=	synonymous_variant	1/4	ENST00000315520.10	NP_001643.2
LOC105369764	XR_001749143.2 linkuse as main transcript	n.208+2068A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
AQP6	ENST00000315520.10 linkuse as main transcript	c.57T>C	p.Leu19=	synonymous_variant	1/4	1	NM_001652.4	ENSP00000320247	P1
AQP6	ENST00000489786.5 linkuse as main transcript	n.2070T>C		non_coding_transcript_exon_variant	4/7	1
AQP6	ENST00000618286.1 linkuse as main transcript	c.57T>C	p.Leu19=	synonymous_variant	1/2	5		ENSP00000477759
AQP6	ENST00000551733.5 linkuse as main transcript	c.-121+695T>C		intron_variant		3		ENSP00000449830

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3879

AN:

152194

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0877

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00425

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00755

AC:

1895

AN:

251060

Hom.:

AF XY:

0.00574

AC XY:

779

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.0939

Gnomad AMR exome

AF:

0.00486

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00565

Gnomad SAS exome

AF:

0.000589

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00289

AC:

4217

AN:

1461572

Hom.:

137

Cov.:

AF XY:

0.00249

AC XY:

1811

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.0896

Gnomad4 AMR exome

AF:

0.00543

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00360

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.000229

Gnomad4 OTH exome

AF:

0.00724

GnomAD4 genome

AF:

0.0255

AC:

3885

AN:

152312

Hom.:

145

Cov.:

AF XY:

0.0250

AC XY:

1861

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0876

Gnomad4 AMR

AF:

0.00967

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00426

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0295

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

DANN

Benign

0.57

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