Variant 12-49962386-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001651.4(AQP5):c.363+6T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,391,158 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

AQP5
NM_001651.4 splice_region, intron

Scores

Splicing: ADA: 0.3655

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.29

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 12-49962386-T-G is Benign according to our data. Variant chr12-49962386-T-G is described in ClinVar as [Benign]. Clinvar id is 731677.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00498 (98/19666) while in subpopulation NFE AF= 0.0207 (89/4298). AF 95% confidence interval is 0.0172. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High AC in GnomAd4 at 98 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP5	NM_001651.4 link	c.363+6T>G		splice_region_variant, intron_variant		ENST00000293599.7	NP_001642.1	P55064

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AQP5	ENST00000293599.7 link	c.363+6T>G	splice_region_variant, intron_variant	1	NM_001651.4	ENSP00000293599.5	P55064
AQP5-AS1	ENST00000550214.1 link	n.258+281A>C	intron_variant	2
AQP5-AS1	ENST00000550530.1 link	n.117+281A>C	intron_variant	3
AQP5-AS1	ENST00000552379.1 link	n.256+281A>C	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

AN:

19654

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00803

AC:

176

AN:

21916

Hom.:

AF XY:

0.00771

AC XY:

AN XY:

12446

show subpopulations

Gnomad AFR exome

AF:

0.000830

Gnomad AMR exome

AF:

0.00100

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000623

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00170

AC:

2328

AN:

1371492

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1083

AN XY:

680780

show subpopulations

Gnomad4 AFR exome

AF:

0.000272

Gnomad4 AMR exome

AF:

0.0000495

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000303

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00211

Gnomad4 OTH exome

AF:

0.000856

GnomAD4 genome

AF:

0.00498

AC:

AN:

19666

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

AN XY:

9446

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0207

Gnomad4 OTH

AF:

0.00

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

Jul 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.37

dbscSNV1_RF

Benign

0.43

SpliceAI score (max)

0.030

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