rs1022477

Positions:

• chr22-45426007-G-A
• chr22-45426007-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015653.5(RIBC2):​c.735G>A​(p.Leu245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,612,828 control chromosomes in the GnomAD database, including 226,601 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 (31191 hom., cov: 33)
  • Exomes 𝑓: 0.51 (195410 hom.)
• Consequence: RIBC2 NM_015653.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76

Genes affected

RIBC2 (HGNC:13241): (RIB43A domain with coiled-coils 2) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=2.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC2	NM_015653.5	c.735G>A	p.Leu245=	synonymous_variant	5/7	ENST00000614167.2	NP_056468.3
RIBC2	XM_005261524.5	c.516G>A	p.Leu172=	synonymous_variant	5/7		XP_005261581.1
RIBC2	XM_011530126.3	c.246G>A	p.Leu82=	synonymous_variant	3/5		XP_011528428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC2	ENST00000614167.2	c.735G>A	p.Leu245=	synonymous_variant	5/7	1	NM_015653.5	ENSP00000483356	P1
RIBC2	ENST00000466226.1	n.417G>A		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93632 AN: 151970 Hom.: 31143 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.614

GnomAD3 exomes AF: 0.563 AC: 140851 AN: 250128 Hom.: 41588 AF XY: 0.563 AC XY: 76197 AN XY: 135314

Gnomad AFR exome AF: 0.883

Gnomad AMR exome AF: 0.526

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.704

Gnomad SAS exome AF: 0.677

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.509 AC: 743789 AN: 1460740 Hom.: 195410 Cov.: 56 AF XY: 0.512 AC XY: 372235 AN XY: 726610

Gnomad4 AFR exome AF: 0.890

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.631

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.477

Gnomad4 OTH exome AF: 0.552

GnomAD4 genome AF: 0.616 AC: 93740 AN: 152088 Hom.: 31191 Cov.: 33 AF XY: 0.619 AC XY: 46047 AN XY: 74348

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.618

Alfa AF: 0.520 Hom.: 35502

Bravo AF: 0.631

Asia WGS AF: 0.751 AC: 2613 AN: 3478

EpiCase AF: 0.497

EpiControl AF: 0.516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.62

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: rs1022477; hg19: chr22-45821887;