rs457860

Positions:

• chr18-26878241-A-C
• chr18-26878241-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_026908.1(AQP4-AS1):​n.53+12881A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,142 control chromosomes in the GnomAD database, including 68,854 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 0.95 (68854 hom., cov: 30)
• Consequence: AQP4-AS1 NR_026908.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP4-AS1	NR_026908.1	n.53+12881A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP4-AS1	ENST00000578701.5	n.54+12881A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144591 AN: 152024 Hom.: 68789 Cov.: 30

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.951 AC: 144715 AN: 152142 Hom.: 68854 Cov.: 30 AF XY: 0.950 AC XY: 70634 AN XY: 74362

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.976

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.960

Alfa AF: 0.944 Hom.: 8413

Bravo AF: 0.959

Asia WGS AF: 0.976 AC: 3394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.28
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs457860; hg19: chr18-24458205;