7-30919387-T-C

Variant names:

• chr7-30919387-T-C
• rs17159702
• NM_198098.4:c.385-2679T>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.385-2679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,998 control chromosomes in the GnomAD database, including 15,333 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 0.41 (15333 hom., cov: 32)
• Consequence: AQP1 NM_198098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 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.385-2679T>C		intron	N/A	NP_932766.1
	AQP1	NM_001329872.2		c.385-2679T>C		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.385-2679T>C		intron	N/A	ENSP00000311165.4
	ENSG00000250424	ENST00000509504.2	TSL:5	c.922-2679T>C		intron	N/A	ENSP00000421315.2
	AQP1	ENST00000441328.7	TSL:1	n.196-4494T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62835 AN: 151880 Hom.: 15302 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.414 AC: 62919 AN: 151998 Hom.: 15333 Cov.: 32 AF XY: 0.417 AC XY: 30996 AN XY: 74318

African (AFR) AF: 0.687 AC: 28463 AN: 41430

American (AMR) AF: 0.378 AC: 5779 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3472

East Asian (EAS) AF: 0.457 AC: 2359 AN: 5164

South Asian (SAS) AF: 0.345 AC: 1660 AN: 4806

European-Finnish (FIN) AF: 0.336 AC: 3555 AN: 10574

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18964 AN: 67960

Other (OTH) AF: 0.390 AC: 822 AN: 2108

Alfa AF: 0.331 Hom.: 30901

Bravo AF: 0.429

Asia WGS AF: 0.418 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-0.086
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: rs17159702; hg19: chr7-30959002;