22-45413743-C-A

Position:

• chr22-45413743-C-A

Variant summary

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

The NM_015653.5(RIBC2):​c.-144C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,266,372 control chromosomes in the GnomAD database, including 127,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (21255 hom., cov: 34)
  • Exomes 𝑓: 0.43 (106446 hom.)
• Consequence: RIBC2 NM_015653.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.516

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 22-45413743-C-A is Benign according to our data. Variant chr22-45413743-C-A is described in ClinVar as [Benign]. Clinvar id is 1241132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIBC2	NM_015653.5	c.-144C>A		5_prime_UTR_variant	1/7	ENST00000614167.2
RIBC2	XM_017028766.2	c.-144C>A		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIBC2	ENST00000614167.2	c.-144C>A		5_prime_UTR_variant	1/7	1	NM_015653.5	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77676 AN: 152048 Hom.: 21213 Cov.: 34

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.431 AC: 480049 AN: 1114206 Hom.: 106446 Cov.: 15 AF XY: 0.433 AC XY: 236814 AN XY: 547092

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.411

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.567

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.511 AC: 77776 AN: 152166 Hom.: 21255 Cov.: 34 AF XY: 0.515 AC XY: 38307 AN XY: 74406

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.502

Alfa AF: 0.382 Hom.: 1997

Bravo AF: 0.516

Asia WGS AF: 0.621 AC: 2161 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	This variant is associated with the following publications: (PMID: 32329860) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.4
DANN	Benign	0.66

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: rs2272804; hg19: chr22-45809624; COSMIC: COSV61581714; COSMIC: COSV61581714;