12-49964271-A-G

Variant names:

• chr12-49964271-A-G
• rs3736309
• NM_001651.4:c.612+96A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001651.4(AQP5):​c.612+96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,358,490 control chromosomes in the GnomAD database, including 18,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1527 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17298 hom.)
• Consequence: AQP5 NM_001651.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.132
• Publications: 23 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)

LOC105369764 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-49964271-A-G is Benign according to our data. Variant chr12-49964271-A-G is described in ClinVar as Benign. ClinVar VariationId is 1276842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP5	NM_001651.4	c.612+96A>G		intron_variant	Intron 3 of 3	ENST00000293599.7	NP_001642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP5	ENST00000293599.7	c.612+96A>G		intron_variant	Intron 3 of 3	1	NM_001651.4	ENSP00000293599.5
AQP5	ENST00000553132.1	n.601+96A>G		intron_variant	Intron 1 of 1	2
AQP5-AS1	ENST00000750790.1	n.301+1412T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18507 AN: 152084 Hom.: 1529 Cov.: 33

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.159 AC: 192121 AN: 1206288 Hom.: 17298 AF XY: 0.163 AC XY: 99323 AN XY: 607766

African (AFR) AF: 0.0254 AC: 717 AN: 28244

American (AMR) AF: 0.0739 AC: 2999 AN: 40596

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 4821 AN: 23964

East Asian (EAS) AF: 0.356 AC: 13377 AN: 37554

South Asian (SAS) AF: 0.239 AC: 18845 AN: 78984

European-Finnish (FIN) AF: 0.136 AC: 6812 AN: 49954

Middle Eastern (MID) AF: 0.212 AC: 1120 AN: 5276

European-Non Finnish (NFE) AF: 0.151 AC: 134697 AN: 889866

Other (OTH) AF: 0.168 AC: 8733 AN: 51850

GnomAD4 genome AF: 0.122 AC: 18500 AN: 152202 Hom.: 1527 Cov.: 33 AF XY: 0.122 AC XY: 9085 AN XY: 74406

African (AFR) AF: 0.0296 AC: 1231 AN: 41548

American (AMR) AF: 0.0900 AC: 1376 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1801 AN: 5162

South Asian (SAS) AF: 0.242 AC: 1165 AN: 4820

European-Finnish (FIN) AF: 0.127 AC: 1347 AN: 10594

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10312 AN: 67996

Other (OTH) AF: 0.138 AC: 292 AN: 2116

Alfa AF: 0.135 Hom.: 1366

Bravo AF: 0.113

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.81
PhyloP100		-0.13
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: rs3736309; hg19: chr12-50358054; COSMIC: COSV107356582; COSMIC: COSV107356582;