X-53422829-C-T

Position:

• chrX-53422829-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000329209.9(RIBC1):​c.-181C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 362,286 control chromosomes in the GnomAD database, including 405 homozygotes. There are 4,801 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (126 hom., 1375 hem., cov: 24)
  • Exomes 𝑓: 0.049 (279 hom. 3426 hem.)
• Consequence: RIBC1 ENST00000329209.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.333

Genes affected

RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant X-53422829-C-T is Benign according to our data. Variant chrX-53422829-C-T is described in ClinVar as [Benign]. Clinvar id is 1226124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5			upstream_gene_variant		ENST00000375327.6	NP_001026915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000329209.9	c.-181C>T		5_prime_UTR_variant	1/5	3		ENSP00000332142
RIBC1	ENST00000375327.6			upstream_gene_variant		1	NM_001031745.5	ENSP00000364476	P1
RIBC1	ENST00000414955.6			upstream_gene_variant		2		ENSP00000401463

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 4680 AN: 112917 Hom.: 126 Cov.: 24 AF XY: 0.0393 AC XY: 1376 AN XY: 35055

Gnomad AFR AF: 0.00880

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0226

Gnomad EAS AF: 0.00112

Gnomad SAS AF: 0.00610

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0167

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0361

GnomAD4 exome AF: 0.0488 AC: 12179 AN: 249318 Hom.: 279 Cov.: 0 AF XY: 0.0457 AC XY: 3426 AN XY: 74946

Gnomad4 AFR exome AF: 0.00946

Gnomad4 AMR exome AF: 0.0216

Gnomad4 ASJ exome AF: 0.0250

Gnomad4 EAS exome AF: 0.0000630

Gnomad4 SAS exome AF: 0.00776

Gnomad4 FIN exome AF: 0.0611

Gnomad4 NFE exome AF: 0.0665

Gnomad4 OTH exome AF: 0.0476

GnomAD4 genome AF: 0.0414 AC: 4678 AN: 112968 Hom.: 126 Cov.: 24 AF XY: 0.0392 AC XY: 1375 AN XY: 35116

Gnomad4 AFR AF: 0.00878

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.0226

Gnomad4 EAS AF: 0.00112

Gnomad4 SAS AF: 0.00611

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.0357

Alfa AF: 0.0482 Hom.: 267

Bravo AF: 0.0389

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.8
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs186837286; hg19: chrX-53449778;