15-34935412-T-C

Variant summary

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

The NM_014691.3(AQR):c.719-777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,974 control chromosomes in the GnomAD database, including 31,036 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 0.62 (31036 hom., cov: 32)
• Consequence: AQR NM_014691.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

Genes affected

AQR (HGNC:29513): (aquarius intron-binding spliceosomal factor) Enables 3'-5' RNA helicase activity and single-stranded RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQR	NM_014691.3	c.719-777A>G		intron_variant		ENST00000156471.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQR	ENST00000156471.10	c.719-777A>G		intron_variant		1	NM_014691.3	P1
AQR	ENST00000543879.6	c.719-777A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93842 AN: 151856 Hom.: 31025 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.618 AC: 93885 AN: 151974 Hom.: 31036 Cov.: 32 AF XY: 0.620 AC XY: 46018 AN XY: 74268

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.625

Alfa AF: 0.702 Hom.: 15014

Bravo AF: 0.589

Asia WGS AF: 0.670 AC: 2326 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.8
Dann	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs963425; hg19: chr15-35227613;