Variant rs2273913 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.00

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.246C>T	p.Tyr82=	synonymous_variant	2/21	ENST00000324103.11
RNF31	NM_001310332.2 linkuse as main transcript	c.-272C>T		5_prime_UTR_variant	2/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF31	ENST00000324103.11 linkuse as main transcript	c.246C>T	p.Tyr82=	synonymous_variant	2/21	1	NM_017999.5	P1	Q96EP0-1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39228

AN:

152032

Hom.:

5719

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.221

AC XY:

160884

AN XY:

727238

show subpopulations

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.:

AF XY:

0.260

AC XY:

19356

AN XY:

74366

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over