Variant chr12-49965105-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001651.4(AQP5):c.726G>A(p.Thr242=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,614,018 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 32)

Exomes 𝑓: 0.015 ( 214 hom. )

Consequence

AQP5
NM_001651.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.71

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 12-49965105-G-A is Benign according to our data. Variant chr12-49965105-G-A is described in ClinVar as [Benign]. Clinvar id is 1562092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.71 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.012 (1826/152308) while in subpopulation NFE AF= 0.0166 (1127/68026). AF 95% confidence interval is 0.0158. There are 18 homozygotes in gnomad4. There are 892 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1826 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP5	NM_001651.4 linkuse as main transcript	c.726G>A	p.Thr242=	synonymous_variant	4/4	ENST00000293599.7
LOC105369764	XR_001749143.2 linkuse as main transcript	n.332-186C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP5	ENST00000293599.7 linkuse as main transcript	c.726G>A	p.Thr242=	synonymous_variant	4/4	1	NM_001651.4	P1
AQP5	ENST00000553132.1 linkuse as main transcript	n.715G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1828

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00347

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0205

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0126

AC:

3171

AN:

251084

Hom.:

AF XY:

0.0123

AC XY:

1677

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00692

Gnomad ASJ exome

AF:

0.0544

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.0214

Gnomad NFE exome

AF:

0.0151

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.0154

AC:

22538

AN:

1461710

Hom.:

214

Cov.:

AF XY:

0.0151

AC XY:

11010

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.00711

Gnomad4 ASJ exome

AF:

0.0517

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00284

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0120

AC:

1826

AN:

152308

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

892

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00346

Gnomad4 AMR

AF:

0.00738

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0205

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0160

EpiControl

AF:

0.0145

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	Jan 18, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.31

DANN

Benign

0.84

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