NM_001650.7:c.32+641C>T

Variant names:

• chr18-26865017-G-A
• rs4800773
• NM_001650.7:c.32+641C>T

Variant summary

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

The NM_001650.7(AQP4):​c.32+641C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,298 control chromosomes in the GnomAD database, including 10,615 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 0.37 (10615 hom., cov: 30)
• Consequence: AQP4 NM_001650.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP4	NM_001650.7	MANE Select	c.32+641C>T		intron	N/A	NP_001641.1
	AQP4	NM_001317384.3		c.32+641C>T		intron	N/A	NP_001304313.1
	AQP4	NM_001364287.1		c.-35+641C>T		intron	N/A	NP_001351216.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP4	ENST00000383168.9	TSL:1 MANE Select	c.32+641C>T		intron	N/A	ENSP00000372654.4
	AQP4	ENST00000672981.2		c.32+641C>T		intron	N/A	ENSP00000500598.2
	AQP4	ENST00000672188.1		c.32+641C>T		intron	N/A	ENSP00000500720.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 55883 AN: 151190 Hom.: 10607 Cov.: 30

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.370 AC: 55931 AN: 151298 Hom.: 10615 Cov.: 30 AF XY: 0.365 AC XY: 26980 AN XY: 73856

African (AFR) AF: 0.432 AC: 17819 AN: 41222

American (AMR) AF: 0.326 AC: 4963 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3470

East Asian (EAS) AF: 0.165 AC: 851 AN: 5160

South Asian (SAS) AF: 0.250 AC: 1192 AN: 4766

European-Finnish (FIN) AF: 0.382 AC: 3928 AN: 10288

Middle Eastern (MID) AF: 0.344 AC: 99 AN: 288

European-Non Finnish (NFE) AF: 0.368 AC: 25000 AN: 67856

Other (OTH) AF: 0.337 AC: 709 AN: 2106

Alfa AF: 0.356 Hom.: 9775

Bravo AF: 0.369

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.21
PhyloP100		-0.38
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: rs4800773; hg19: chr18-24444981;