15-34935412-T-C

Variant names:

• chr15-34935412-T-C
• rs963425
• NM_014691.3:c.719-777A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014691.3. 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
	AQR	NM_014691.3	MANE Select	c.719-777A>G		intron	N/A	NP_055506.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQR	ENST00000156471.10	TSL:1 MANE Select	c.719-777A>G		intron	N/A	ENSP00000156471.5
	AQR	ENST00000543879.6	TSL:2	n.719-777A>G		intron	N/A	ENSP00000445700.2

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

African (AFR) AF: 0.370 AC: 15330 AN: 41444

American (AMR) AF: 0.578 AC: 8820 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2474 AN: 3472

East Asian (EAS) AF: 0.632 AC: 3273 AN: 5176

South Asian (SAS) AF: 0.751 AC: 3626 AN: 4826

European-Finnish (FIN) AF: 0.787 AC: 8319 AN: 10574

Middle Eastern (MID) AF: 0.672 AC: 195 AN: 290

European-Non Finnish (NFE) AF: 0.735 AC: 49922 AN: 67916

Other (OTH) AF: 0.625 AC: 1320 AN: 2112

Alfa AF: 0.690 Hom.: 22670

Bravo AF: 0.589

Asia WGS AF: 0.670 AC: 2326 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.81
PhyloP100		-0.19
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: rs963425; hg19: chr15-35227613;