rs41308104

chr12-49965105-G-Achr12-49965105-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.71

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]

LOC105369764 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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. This position pass quality control queck.
• BS2: High AC in GnomAd at 1828 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP5	NM_001651.4	c.726G>A	p.Thr242=	synonymous_variant	4/4	ENST00000293599.7
LOC105369764	XR_001749143.2	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	c.726G>A	p.Thr242=	synonymous_variant	4/4	1	NM_001651.4	P1
AQP5	ENST00000553132.1	n.715G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1828 AN: 152190 Hom.: 18 Cov.: 32

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.: 31 AF XY: 0.0123 AC XY: 1677 AN XY: 135796

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.: 33 AF XY: 0.0151 AC XY: 11010 AN XY: 727158

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.: 18 Cov.: 32 AF XY: 0.0120 AC XY: 892 AN XY: 74480

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.: 13

Bravo AF: 0.0108

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0160

EpiControl AF: 0.0145

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs41308104; hg19: chr12-50358888;