7-30921380-G-A

Variant names:

• chr7-30921380-G-A
• rs2267720
• NM_198098.4:c.385-686G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198098.4(AQP1):​c.385-686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 1,405,316 control chromosomes in the GnomAD database, including 3,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (882 hom., cov: 33)
  • Exomes 𝑓: 0.054 (2866 hom.)
• Consequence: AQP1 NM_198098.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0810
• Publications: 1 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: ClinGen, Ambry Genetics

ENSG00000250424 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-30921380-G-A is Benign according to our data. Variant chr7-30921380-G-A is described in ClinVar as Benign. ClinVar VariationId is 1223959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP1	NM_198098.4	MANE Select	c.385-686G>A		intron	N/A	NP_932766.1	P29972-1
	AQP1	NM_001329872.2		c.385-686G>A		intron	N/A	NP_001316801.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP1	ENST00000311813.11	TSL:1 MANE Select	c.385-686G>A		intron	N/A	ENSP00000311165.4	P29972-1
	ENSG00000250424	ENST00000509504.2	TSL:5	c.922-686G>A		intron	N/A	ENSP00000421315.2	K7N7A8
	AQP1	ENST00000441328.7	TSL:1	n.196-2501G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13776 AN: 152080 Hom.: 880 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0872

GnomAD4 exome AF: 0.0536 AC: 67218 AN: 1253118 Hom.: 2866 Cov.: 30 AF XY: 0.0548 AC XY: 33035 AN XY: 603072

African (AFR) AF: 0.166 AC: 4610 AN: 27852

American (AMR) AF: 0.0650 AC: 1237 AN: 19042

Ashkenazi Jewish (ASJ) AF: 0.0575 AC: 1056 AN: 18350

East Asian (EAS) AF: 0.221 AC: 7513 AN: 34066

South Asian (SAS) AF: 0.105 AC: 5385 AN: 51430

European-Finnish (FIN) AF: 0.0450 AC: 1371 AN: 30472

Middle Eastern (MID) AF: 0.106 AC: 385 AN: 3620

European-Non Finnish (NFE) AF: 0.0414 AC: 42106 AN: 1016146

Other (OTH) AF: 0.0682 AC: 3555 AN: 52140

GnomAD4 genome AF: 0.0905 AC: 13781 AN: 152198 Hom.: 882 Cov.: 33 AF XY: 0.0926 AC XY: 6894 AN XY: 74414

African (AFR) AF: 0.161 AC: 6687 AN: 41498

American (AMR) AF: 0.0695 AC: 1063 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3472

East Asian (EAS) AF: 0.246 AC: 1269 AN: 5160

South Asian (SAS) AF: 0.124 AC: 599 AN: 4822

European-Finnish (FIN) AF: 0.0497 AC: 527 AN: 10612

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0448 AC: 3049 AN: 68016

Other (OTH) AF: 0.0872 AC: 184 AN: 2110

Alfa AF: 0.0673 Hom.: 715

Bravo AF: 0.0953

Asia WGS AF: 0.158 AC: 550 AN: 3478

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
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		0.081
PromoterAI		0.052	Neutral
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: rs2267720; hg19: chr7-30960995;