Variant 12-49962394-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001651.4(AQP5):c.363+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 81 hom., cov: 0)

Exomes 𝑓: 0.028 ( 88 hom. )

Consequence

AQP5
NM_001651.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.200

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:

AQP5-AS1 (HGNC:55474): (AQP5 and AQP2 antisense RNA 2)

AQP5-AS1 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 (BayesDel_noAF=-0.85).

BP6

Variant 12-49962394-G-A is Benign according to our data. Variant chr12-49962394-G-A is described in ClinVar as [Benign]. Clinvar id is 1221931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP5	NM_001651.4 link	c.363+14G>A		intron_variant		ENST00000293599.7	NP_001642.1	P55064

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AQP5	ENST00000293599.7 link	c.363+14G>A	intron_variant	1	NM_001651.4	ENSP00000293599.5	P55064
AQP5-AS1	ENST00000550214.1 link	n.258+273C>T	intron_variant	2
AQP5-AS1	ENST00000550530.1 link	n.117+273C>T	intron_variant	3
AQP5-AS1	ENST00000552379.1 link	n.256+273C>T	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

2381

AN:

19256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0989

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0238

Gnomad NFE

AF:

0.00370

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.00516

AC:

745

AN:

144282

Hom.:

AF XY:

0.00404

AC XY:

320

AN XY:

79216

show subpopulations

Gnomad AFR exome

AF:

0.0708

Gnomad AMR exome

AF:

0.00302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000187

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.00372

GnomAD4 exome

AF:

0.0283

AC:

2311

AN:

81588

Hom.:

Cov.:

AF XY:

0.0240

AC XY:

993

AN XY:

41386

show subpopulations

Gnomad4 AFR exome

AF:

0.187

Gnomad4 AMR exome

AF:

0.0805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000846

Gnomad4 FIN exome

AF:

0.000849

Gnomad4 NFE exome

AF:

0.00202

Gnomad4 OTH exome

AF:

0.0479

GnomAD4 genome

AF:

0.124

AC:

2385

AN:

19268

Hom.:

Cov.:

AF XY:

0.123

AC XY:

1162

AN XY:

9416

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.0983

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00370

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.000438

Hom.:

Bravo

AF:

0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2025	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.3

DANN

Benign

0.89

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