rs1058427

Variant names:

• chr18-26855131-G-T
• rs1058427
• NM_001650.7:c.*1080C>A

Variant summary

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

The NM_001650.7(AQP4):​c.*1080C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,252 control chromosomes in the GnomAD database, including 816 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 0.087 (816 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AQP4 NM_001650.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 5 publications found

Genes affected

AQP4 (HGNC:637): (aquaporin 4) This gene encodes a member of the aquaporin family of intrinsic membrane proteins that function as water-selective channels in the plasma membranes of many cells. This protein is the predominant aquaporin found in brain and has an important role in brain water homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. Additional isoforms, resulting from the use of alternative in-frame translation initiation codons, have also been described. Recent studies provided evidence for translational readthrough in this gene, and expression of C-terminally extended isoforms via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Jun 2018]

AQP4-AS1 (HGNC:26399): (AQP4 antisense RNA 1)

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 (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001650.7. 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
	AQP4	NM_001650.7	MANE Select	c.*1080C>A		3_prime_UTR	Exon 5 of 5	NP_001641.1	F1DSG4
	AQP4	NM_001317384.3		c.*993C>A		3_prime_UTR	Exon 5 of 5	NP_001304313.1	A0A5F9ZHR4
	AQP4	NM_001364287.1		c.*993C>A		3_prime_UTR	Exon 5 of 5	NP_001351216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP4	ENST00000383168.9	TSL:1 MANE Select	c.*1080C>A		3_prime_UTR	Exon 5 of 5	ENSP00000372654.4	P55087-1
	AQP4	ENST00000672981.2		c.*993C>A		3_prime_UTR	Exon 5 of 5	ENSP00000500598.2	A0A5F9ZHR4
	AQP4	ENST00000672188.1		c.*1080C>A		3_prime_UTR	Exon 5 of 5	ENSP00000500720.1	P55087-1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13305 AN: 152134 Hom.: 816 Cov.: 33

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0929

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0874 AC: 13303 AN: 152252 Hom.: 816 Cov.: 33 AF XY: 0.0872 AC XY: 6495 AN XY: 74444

African (AFR) AF: 0.0224 AC: 931 AN: 41568

American (AMR) AF: 0.0945 AC: 1445 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3468

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5194

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4824

European-Finnish (FIN) AF: 0.157 AC: 1658 AN: 10588

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8353 AN: 68002

Other (OTH) AF: 0.0919 AC: 194 AN: 2110

Alfa AF: 0.113 Hom.: 938

Bravo AF: 0.0803

Asia WGS AF: 0.0170 AC: 61 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	3.0
DANN	Benign	0.69
PhyloP100		0.17
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: rs1058427; hg19: chr18-24435095;