Genetic Variant AQP5:c.612+96A>G (chr12-49964271-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001651.4(AQP5):c.612+96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,358,490 control chromosomes in the GnomAD database, including 18,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1527 hom., cov: 33)

Exomes 𝑓: 0.16 ( 17298 hom. )

Consequence

AQP5
NM_001651.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.132

Variant links:

Genes affected

AQP5 (HGNC:638): (aquaporin 5) Aquaporin 5 (AQP5) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 5 plays a role in the generation of saliva, tears and pulmonary secretions. AQP0, AQP2, AQP5, and AQP6 are closely related and all map to 12q13. [provided by RefSeq, Jul 2008]

AQP5 links:

LOC105369764 (HGNC:):

LOC105369764 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-49964271-A-G is Benign according to our data. Variant chr12-49964271-A-G is described in ClinVar as [Benign]. Clinvar id is 1276842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP5	NM_001651.4 link	c.612+96A>G		intron_variant	Intron 3 of 3	ENST00000293599.7	NP_001642.1	P55064

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP5	ENST00000293599.7 link	c.612+96A>G		intron_variant	Intron 3 of 3	1	NM_001651.4	ENSP00000293599.5		P55064
AQP5	ENST00000553132.1 link	n.601+96A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18507

AN:

152084

Hom.:

1529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.0902

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.140

GnomAD4 exome

AF:

0.159

AC:

192121

AN:

1206288

Hom.:

17298

AF XY:

0.163

AC XY:

99323

AN XY:

607766

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.0739

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.239

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.122

AC:

18500

AN:

152202

Hom.:

1527

Cov.:

AF XY:

0.122

AC XY:

9085

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.0900

Gnomad4 ASJ

AF:

0.203

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.144

Hom.:

1076

Bravo

AF:

0.113

Asia WGS

AF:

0.219

AC:

763

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.2

DANN

Benign

0.81

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