12-49964391-C-A

Position:

• chr12-49964391-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001651.4(AQP5):​c.612+216C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,956 control chromosomes in the GnomAD database, including 5,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (5051 hom., cov: 31)
• Consequence: AQP5 NM_001651.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.61

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-49964391-C-A is Benign according to our data. Variant chr12-49964391-C-A is described in ClinVar as [Benign]. Clinvar id is 1225148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP5	NM_001651.4	c.612+216C>A		intron_variant		ENST00000293599.7	NP_001642.1
AQP5	XM_005268838.3	c.612+216C>A		intron_variant			XP_005268895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP5	ENST00000293599.7	c.612+216C>A		intron_variant		1	NM_001651.4	ENSP00000293599	P1
AQP5	ENST00000553132.1	n.601+216C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33952 AN: 151836 Hom.: 5042 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 33999 AN: 151956 Hom.: 5051 Cov.: 31 AF XY: 0.220 AC XY: 16343 AN XY: 74282

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.0944

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.197

Alfa AF: 0.137 Hom.: 708

Bravo AF: 0.236

Asia WGS AF: 0.145 AC: 508 AN: 3478

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

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.020
DANN	Benign	0.59

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: rs923911; hg19: chr12-50358174;