12-49962391-TGGGG-TGGGGG

Variant names:

• chr12-49962391-T-TG
• rs3832811
• NM_001651.4:c.363+21dupG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001651.4(AQP5):​c.363+21dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 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 VariationId is 1598957.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP5	NM_001651.4	MANE Select	c.363+21dupG		intron	N/A	NP_001642.1	P55064
	AQP5-AS1	NR_110589.1		n.258+275dupC		intron	N/A
	AQP5-AS1	NR_110590.1		n.256+275dupC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP5	ENST00000293599.7	TSL:1 MANE Select	c.363+11_363+12insG		intron	N/A	ENSP00000293599.5	P55064
	AQP5	ENST00000857226.1		c.363+11_363+12insG		intron	N/A	ENSP00000527285.1
	AQP5-AS1	ENST00000550214.2	TSL:2	n.286+275_286+276insC		intron	N/A

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

GnomAD2 exomes AF: 0.000388 AC: 66 AN: 170032 AF XY: 0.000359

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0409 AC: 1157 AN: 28300

American (AMR) AF: 0.000508 AC: 19 AN: 37426

Ashkenazi Jewish (ASJ) AF: 0.000958 AC: 22 AN: 22958

East Asian (EAS) AF: 0.0174 AC: 598 AN: 34348

South Asian (SAS) AF: 0.000480 AC: 37 AN: 77136

European-Finnish (FIN) AF: 0.000318 AC: 12 AN: 37770

Middle Eastern (MID) AF: 0.00339 AC: 13 AN: 3832

European-Non Finnish (NFE) AF: 0.00118 AC: 1277 AN: 1082782

Other (OTH) AF: 0.00508 AC: 287 AN: 56540

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0847 AC: 3345 AN: 39492

American (AMR) AF: 0.00938 AC: 143 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3464

East Asian (EAS) AF: 0.107 AC: 524 AN: 4904

South Asian (SAS) AF: 0.00462 AC: 22 AN: 4766

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10552

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 67858

Other (OTH) AF: 0.0182 AC: 38 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000448 Hom.: 366

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3832811; hg19: chr12-50356174;