rs3763043

Variant names:

• chr18-26855854-C-A
• rs3763043
• NM_001650.7:c.*357G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-26855854-C-A
• chr18-26855854-C-G
• chr18-26855854-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001650.7(AQP4):​c.*357G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: AQP4 NM_001650.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP4	NM_001650.7	c.*357G>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000383168.9	NP_001641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP4	ENST00000383168.9	c.*357G>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001650.7	ENSP00000372654.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000658 AC: 1 AN: 151998 Hom.: 0 Cov.: 0 AF XY: 0.0000122 AC XY: 1 AN XY: 81662

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4286

American (AMR) AF: 0.00 AC: 0 AN: 5834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3922

East Asian (EAS) AF: 0.00 AC: 0 AN: 6586

South Asian (SAS) AF: 0.00 AC: 0 AN: 25230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 584

European-Non Finnish (NFE) AF: 0.0000111 AC: 1 AN: 90144

Other (OTH) AF: 0.00 AC: 0 AN: 7688

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.42
PhyloP100		0.38

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: rs3763043; hg19: chr18-24435818;