rs2273913

chr14-24148029-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017999.5(RNF31):c.246C>T(p.Tyr82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,614,022 control chromosomes in the GnomAD database, including 44,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5725 hom., cov: 33)
  • Exomes 𝑓: 0.22 (38721 hom.)
• Consequence: RNF31 NM_017999.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00

Genes affected

RNF31 (HGNC:16031): (ring finger protein 31) The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The encoded protein is the E3 ubiquitin-protein ligase component of the linear ubiquitin chain assembly complex. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 14-24148029-C-T is Benign according to our data. Variant chr14-24148029-C-T is described in ClinVar as [Benign]. Clinvar id is 1165355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF31	NM_017999.5	c.246C>T	p.Tyr82=	synonymous_variant	2/21	ENST00000324103.11
RNF31	NM_001310332.2	c.-272C>T		5_prime_UTR_variant	2/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF31	ENST00000324103.11	c.246C>T	p.Tyr82=	synonymous_variant	2/21	1	NM_017999.5	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39228 AN: 152032 Hom.: 5719 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.232

GnomAD3 exomes AF: 0.246 AC: 61317 AN: 249498 Hom.: 8794 AF XY: 0.244 AC XY: 32987 AN XY: 135392

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.0905

Gnomad EAS exome AF: 0.545

Gnomad SAS exome AF: 0.293

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.220 AC: 321408 AN: 1461872 Hom.: 38721 Cov.: 35 AF XY: 0.221 AC XY: 160884 AN XY: 727238

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.0898

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.258 AC: 39247 AN: 152150 Hom.: 5725 Cov.: 33 AF XY: 0.260 AC XY: 19356 AN XY: 74366

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.234

Alfa AF: 0.210 Hom.: 4512

Bravo AF: 0.260

Asia WGS AF: 0.395 AC: 1374 AN: 3476

EpiCase AF: 0.192

EpiControl AF: 0.187

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 42% of patients studied by a panel of primary immunodeficiencies. Number of patients: 40. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.2
Dann	Benign	0.93

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: rs2273913; hg19: chr14-24617238; COSMIC: COSV53760109; COSMIC: COSV53760109;