rs10516559

Variant names:

• chr4-109825574-T-C
• rs10516559
• ENST00000863519.1:c.*1143T>C

Variant summary

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

The ENST00000863519.1(GAR1):​c.*1143T>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 152,242 control chromosomes in the GnomAD database, including 857 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 0.097 (857 hom., cov: 32)
• Consequence: GAR1 ENST00000863519.1 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 9 publications found

Genes affected

GAR1 (HGNC:14264): (GAR1 ribonucleoprotein) This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the DKC1, NOLA2 and NOLA3 proteins. These four H/ACA snoRNP proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. These four H/ACA snoRNP proteins are also components of the telomerase complex. The encoded protein of this gene contains two glycine- and arginine-rich domains and is related to Saccharomyces cerevisiae Gar1p. Two splice variants have been found for this gene. [provided by RefSeq, Jul 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000863519.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAR1	ENST00000863519.1		c.*1143T>C		splice_region	Exon 7 of 7	ENSP00000533578.1
	GAR1	ENST00000863519.1		c.*1143T>C		3_prime_UTR	Exon 7 of 7	ENSP00000533578.1
	GAR1	ENST00000958032.1		c.*1143T>C		downstream_gene	N/A	ENSP00000628091.1

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14801 AN: 152124 Hom.: 852 Cov.: 32

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0949

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

GnomAD4 genome AF: 0.0973 AC: 14818 AN: 152242 Hom.: 857 Cov.: 32 AF XY: 0.0972 AC XY: 7235 AN XY: 74426

African (AFR) AF: 0.0551 AC: 2289 AN: 41570

American (AMR) AF: 0.154 AC: 2350 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 418 AN: 3472

East Asian (EAS) AF: 0.0713 AC: 369 AN: 5178

South Asian (SAS) AF: 0.0934 AC: 451 AN: 4830

European-Finnish (FIN) AF: 0.106 AC: 1126 AN: 10584

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7545 AN: 68004

Other (OTH) AF: 0.0963 AC: 203 AN: 2108

Alfa AF: 0.111 Hom.: 266

Bravo AF: 0.0999

Asia WGS AF: 0.0930 AC: 323 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	12
DANN	Benign	0.83
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs10516559; hg19: chr4-110746730;