12-49962391-T-TG

Position:

• chr12-49962391-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001651.4(AQP5):​c.363+21dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (196 hom., cov: 0)
  • Exomes 𝑓: 0.0025 (5 hom.)
• Consequence: AQP5 NM_001651.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.227

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-49962391-T-TG is Benign according to our data. Variant chr12-49962391-T-TG is described in ClinVar as [Benign]. Clinvar id is 1598957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP5	NM_001651.4	c.363+21dup		intron_variant		ENST00000293599.7	NP_001642.1
AQP5-AS1	NR_110591.1	n.117+275_117+276insC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP5	ENST00000293599.7	c.363+21dup		intron_variant		1	NM_001651.4	ENSP00000293599	P1
AQP5-AS1	ENST00000550530.1	n.117+275_117+276insC		intron_variant, non_coding_transcript_variant		3
AQP5-AS1	ENST00000550214.1	n.258+275_258+276insC		intron_variant, non_coding_transcript_variant		2
AQP5-AS1	ENST00000552379.1	n.256+275_256+276insC		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4284 AN: 149470 Hom.: 195 Cov.: 0

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.00946

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.00482

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.0184

GnomAD3 exomes AF: 0.000388 AC: 66 AN: 170032 Hom.: 0 AF XY: 0.000359 AC XY: 34 AN XY: 94654

Gnomad AFR exome AF: 0.00269

Gnomad AMR exome AF: 0.000114

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00254

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000109

Gnomad NFE exome AF: 0.0000489

Gnomad OTH exome AF: 0.000471

GnomAD4 exome AF: 0.00248 AC: 3422 AN: 1381092 Hom.: 5 Cov.: 0 AF XY: 0.00228 AC XY: 1555 AN XY: 683224

Gnomad4 AFR exome AF: 0.0409

Gnomad4 AMR exome AF: 0.000508

Gnomad4 ASJ exome AF: 0.000958

Gnomad4 EAS exome AF: 0.0174

Gnomad4 SAS exome AF: 0.000480

Gnomad4 FIN exome AF: 0.000318

Gnomad4 NFE exome AF: 0.00118

Gnomad4 OTH exome AF: 0.00508

GnomAD4 genome AF: 0.0287 AC: 4286 AN: 149574 Hom.: 196 Cov.: 0 AF XY: 0.0281 AC XY: 2057 AN XY: 73090

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.00938

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.00462

Gnomad4 FIN AF: 0.00142

Gnomad4 NFE AF: 0.00243

Gnomad4 OTH AF: 0.0182

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 31, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs3832811; hg19: chr12-50356174;