12-49962391-T-TGG

Position:

• chr12-49962391-T-TGG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001651.4(AQP5):​c.363+20_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 0.0036 (7 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (0 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-49962391-T-TGG is Benign according to our data. Variant chr12-49962391-T-TGG is described in ClinVar as [Benign]. Clinvar id is 2903493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 545 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP5	NM_001651.4	c.363+20_363+21dup		intron_variant		ENST00000293599.7	NP_001642.1
AQP5-AS1	NR_110591.1	n.117+275_117+276insCC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP5	ENST00000293599.7	c.363+20_363+21dup		intron_variant		1	NM_001651.4	ENSP00000293599	P1
AQP5-AS1	ENST00000550530.1	n.117+275_117+276insCC		intron_variant, non_coding_transcript_variant		3
AQP5-AS1	ENST00000550214.1	n.258+275_258+276insCC		intron_variant, non_coding_transcript_variant		2
AQP5-AS1	ENST00000552379.1	n.256+275_256+276insCC		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 543 AN: 149822 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00241

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000964

GnomAD4 exome AF: 0.000143 AC: 198 AN: 1386768 Hom.: 0 Cov.: 0 AF XY: 0.000105 AC XY: 72 AN XY: 685738

Gnomad4 AFR exome AF: 0.00539

Gnomad4 AMR exome AF: 0.0000534

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000660

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.22e-7

Gnomad4 OTH exome AF: 0.000193

GnomAD4 genome AF: 0.00363 AC: 545 AN: 149934 Hom.: 7 Cov.: 0 AF XY: 0.00336 AC XY: 246 AN XY: 73252

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00242

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000954

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

Nov 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;