Genetic Variant NM_001651.4:c.363+18_363+21delGGGG (chr12-49962391-TGGGG-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001651.4(AQP5):c.363+18_363+21delGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,537,206 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00038 ( 11 hom. )

Consequence

AQP5
NM_001651.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.462

Publications

2 publications found

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:

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

AQP5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 12-49962391-TGGGG-T is Benign according to our data. Variant chr12-49962391-TGGGG-T is described in ClinVar as Benign. ClinVar VariationId is 1987458.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 80 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP5	NM_001651.4	MANE Select	c.363+18_363+21delGGGG	intron	N/A	NP_001642.1	P55064
AQP5-AS1	NR_110589.1		n.258+272_258+275delCCCC	intron	N/A
AQP5-AS1	NR_110590.1		n.256+272_256+275delCCCC	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP5	ENST00000293599.7	TSL:1 MANE Select	c.363+12_363+15delGGGG	intron	N/A	ENSP00000293599.5	P55064
AQP5	ENST00000857226.1		c.363+12_363+15delGGGG	intron	N/A	ENSP00000527285.1
AQP5-AS1	ENST00000550214.2	TSL:2	n.286+272_286+275delCCCC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000534

AC:

AN:

149912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00453

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000482

GnomAD2 exomes

AF:

0.00235

AC:

400

AN:

170032

AF XY:

0.00175

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000109

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.000381

AC:

528

AN:

1387182

Hom.:

AF XY:

0.000324

AC XY:

222

AN XY:

685936

show subpopulations

African (AFR)

AF:

0.0000672

AC:

AN:

29776

American (AMR)

AF:

0.0131

AC:

490

AN:

37484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23016

East Asian (EAS)

AF:

0.00

AC:

AN:

36444

South Asian (SAS)

AF:

0.0000389

AC:

AN:

77182

European-Finnish (FIN)

AF:

0.0000529

AC:

AN:

37812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3854

European-Non Finnish (NFE)

AF:

0.0000120

AC:

AN:

1084484

Other (OTH)

AF:

0.000315

AC:

AN:

57130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000533

AC:

AN:

150024

Hom.:

Cov.:

AF XY:

0.000464

AC XY:

AN XY:

73298

show subpopulations

African (AFR)

AF:

0.000201

AC:

AN:

39820

American (AMR)

AF:

0.00452

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

4966

South Asian (SAS)

AF:

0.000210

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67880

Other (OTH)

AF:

0.000477

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000149

Hom.:

366

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over