Variant 12-49973221-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001652.4(AQP6):c.48G>A(p.Ala16Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,650 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 12 hom. )

Consequence

AQP6
NM_001652.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.193

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-49973221-G-A is Benign according to our data. Variant chr12-49973221-G-A is described in ClinVar as [Benign]. Clinvar id is 778590.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.193 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00666 (1014/152352) while in subpopulation AFR AF= 0.0228 (947/41588). AF 95% confidence interval is 0.0216. There are 13 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP6	NM_001652.4 link	c.48G>A	p.Ala16Ala	synonymous_variant	1/4	ENST00000315520.10	NP_001643.2	Q13520
LOC105369764	XR_001749143.2 link	n.208+2077C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AQP6	ENST00000315520.10 link	c.48G>A	p.Ala16Ala	synonymous_variant	1/4	1	NM_001652.4	ENSP00000320247.5	Q13520
AQP6	ENST00000489786.5 link	n.2061G>A		non_coding_transcript_exon_variant	4/7	1
AQP6	ENST00000618286.1 link	c.48G>A	p.Ala16Ala	synonymous_variant	1/2	5		ENSP00000477759.1	Q9NSV5
AQP6	ENST00000551733.5 link	c.-121+686G>A		intron_variant		3		ENSP00000449830.1	F8VW87

Frequencies

GnomAD3 genomes

AF:

0.00663

AC:

1010

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00178

AC:

446

AN:

250716

Hom.:

AF XY:

0.00108

AC XY:

146

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000795

AC:

1162

AN:

1461298

Hom.:

Cov.:

AF XY:

0.000655

AC XY:

476

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.0266

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000836

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00666

AC:

1014

AN:

152352

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

481

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00751

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

DANN

Benign

0.49

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