rs765840

Variant names:

• chr7-30919869-T-A
• rs765840
• NM_198098.4:c.385-2197T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-30919869-T-A
• chr7-30919869-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198098.4(AQP1):​c.385-2197T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,066 control chromosomes in the GnomAD database, including 6,416 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (6416 hom., cov: 32)
• Consequence: AQP1 NM_198098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• Publications: 4 publications found

Genes affected

AQP1 (HGNC:633): (aquaporin 1 (Colton blood group)) This gene encodes a small integral membrane protein with six bilayer spanning domains that functions as a water channel protein. This protein permits passive transport of water along an osmotic gradient. This gene is a possible candidate for disorders involving imbalance in ocular fluid movement. [provided by RefSeq, Aug 2016]

AQP1 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

ENSG00000250424 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198098.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP1	NM_198098.4	MANE Select	c.385-2197T>A		intron	N/A	NP_932766.1
	AQP1	NM_001329872.2		c.385-2197T>A		intron	N/A	NP_001316801.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP1	ENST00000311813.11	TSL:1 MANE Select	c.385-2197T>A		intron	N/A	ENSP00000311165.4
	ENSG00000250424	ENST00000509504.2	TSL:5	c.922-2197T>A		intron	N/A	ENSP00000421315.2
	AQP1	ENST00000441328.7	TSL:1	n.196-4012T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34094 AN: 151948 Hom.: 6400 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34155 AN: 152066 Hom.: 6416 Cov.: 32 AF XY: 0.229 AC XY: 16999 AN XY: 74330

African (AFR) AF: 0.507 AC: 21015 AN: 41430

American (AMR) AF: 0.162 AC: 2474 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1965 AN: 5170

South Asian (SAS) AF: 0.170 AC: 815 AN: 4806

European-Finnish (FIN) AF: 0.157 AC: 1658 AN: 10578

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

European-Non Finnish (NFE) AF: 0.0766 AC: 5209 AN: 68012

Other (OTH) AF: 0.188 AC: 397 AN: 2110

Alfa AF: 0.0685 Hom.: 125

Bravo AF: 0.238

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		0.20
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: rs765840; hg19: chr7-30959484;