rs335929

Variant names:

• chr18-26855623-A-C
• rs335929
• NM_001650.7:c.*588T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-26855623-A-C
• chr18-26855623-A-G
• chr18-26855623-A-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.*588T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 153,808 control chromosomes in the GnomAD database, including 2,423 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 0.16 (2399 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24 hom.)
• Consequence: AQP4 NM_001650.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 22 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 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.*588T>G		3_prime_UTR	Exon 5 of 5	NP_001641.1	F1DSG4
	AQP4	NM_001317384.3		c.*501T>G		3_prime_UTR	Exon 5 of 5	NP_001304313.1	A0A5F9ZHR4
	AQP4	NM_001364287.1		c.*501T>G		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.*588T>G		3_prime_UTR	Exon 5 of 5	ENSP00000372654.4	P55087-1
	AQP4	ENST00000672981.2		c.*501T>G		3_prime_UTR	Exon 5 of 5	ENSP00000500598.2	A0A5F9ZHR4
	AQP4	ENST00000672188.1		c.*588T>G		3_prime_UTR	Exon 5 of 5	ENSP00000500720.1	P55087-1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23723 AN: 152078 Hom.: 2407 Cov.: 33

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.176 AC: 283 AN: 1612 Hom.: 24 Cov.: 0 AF XY: 0.172 AC XY: 150 AN XY: 874

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.103 AC: 22 AN: 214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.250 AC: 3 AN: 12

South Asian (SAS) AF: 0.226 AC: 14 AN: 62

European-Finnish (FIN) AF: 0.186 AC: 79 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.187 AC: 161 AN: 860

Other (OTH) AF: 0.111 AC: 4 AN: 36

GnomAD4 genome AF: 0.156 AC: 23710 AN: 152196 Hom.: 2399 Cov.: 33 AF XY: 0.159 AC XY: 11865 AN XY: 74410

African (AFR) AF: 0.0416 AC: 1730 AN: 41562

American (AMR) AF: 0.132 AC: 2025 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 886 AN: 3466

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5166

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4820

European-Finnish (FIN) AF: 0.156 AC: 1655 AN: 10590

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13190 AN: 67982

Other (OTH) AF: 0.167 AC: 354 AN: 2116

Alfa AF: 0.184 Hom.: 6242

Bravo AF: 0.143

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.48
PhyloP100		-0.32
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: rs335929; hg19: chr18-24435587; COSMIC: COSV67219385; COSMIC: COSV67219385;