rs2273913

Variant names:

• chr14-24148029-C-T
• rs2273913
• ENST00000559275.5:c.-272C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000559275.5(RNF31):​c.-272C>T variant causes a 5 prime UTR premature start codon gain 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 ENST00000559275.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.00
• Publications: 26 publications found

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]

RNF31 Gene-Disease associations (from GenCC):

• autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency 115 with autoinflammation

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000259529 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1165355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
RNF31	NM_017999.5	c.246C>T	p.Tyr82Tyr	synonymous_variant	Exon 2 of 21	ENST00000324103.11	NP_060469.4
RNF31	NM_001310332.2	c.-272C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 21		NP_001297261.1
RNF31	NM_001310332.2	c.-272C>T		5_prime_UTR_variant	Exon 2 of 21		NP_001297261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF31	ENST00000324103.11	c.246C>T	p.Tyr82Tyr	synonymous_variant	Exon 2 of 21	1	NM_017999.5	ENSP00000315112.6
ENSG00000259529	ENST00000558468.2	n.246C>T		non_coding_transcript_exon_variant	Exon 2 of 29	2		ENSP00000457512.2

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

GnomAD2 exomes AF: 0.246 AC: 61317 AN: 249498 AF XY: 0.244

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 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

African (AFR) AF: 0.351 AC: 11749 AN: 33480

American (AMR) AF: 0.219 AC: 9785 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0898 AC: 2348 AN: 26136

East Asian (EAS) AF: 0.533 AC: 21163 AN: 39700

South Asian (SAS) AF: 0.286 AC: 24702 AN: 86258

European-Finnish (FIN) AF: 0.224 AC: 11972 AN: 53412

Middle Eastern (MID) AF: 0.135 AC: 776 AN: 5768

European-Non Finnish (NFE) AF: 0.202 AC: 224924 AN: 1112002

Other (OTH) AF: 0.232 AC: 13989 AN: 60394

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

African (AFR) AF: 0.347 AC: 14408 AN: 41490

American (AMR) AF: 0.218 AC: 3336 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2807 AN: 5160

South Asian (SAS) AF: 0.297 AC: 1434 AN: 4828

European-Finnish (FIN) AF: 0.226 AC: 2396 AN: 10584

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13988 AN: 68000

Other (OTH) AF: 0.234 AC: 494 AN: 2114

Alfa AF: 0.217 Hom.: 6330

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.2
DANN	Benign	0.93
PhyloP100		-2.0
PromoterAI		0.33	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

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