Variant chr17-4942473-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_015528.3(RNF167):c.291+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,613,480 control chromosomes in the GnomAD database, including 243,302 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17069 hom., cov: 31)

Exomes 𝑓: 0.55 ( 226233 hom. )

Consequence

RNF167
NM_015528.3 splice_region, intron

Scores

Splicing: ADA: 0.006805

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

RNF167 (HGNC:24544): (ring finger protein 167) RNF167 is an E3 ubiquitin ligase that interacts with TSSC5 (SLC22A18; MIM 602631) and, together with UBCH6 (UBE2E1; MIM 602916), facilitates TSSC5 polyubiquitylation (Yamada and Gorbsky, 2006 [PubMed 16314844]).[supplied by OMIM, Mar 2008]

RNF167 links:

RNF167 (HGNC:):

RNF167 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 17-4942473-G-A is Benign according to our data. Variant chr17-4942473-G-A is described in ClinVar as [Benign]. Clinvar id is 1238194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF167	NM_015528.3 linkuse as main transcript	c.291+7G>A		splice_region_variant, intron_variant		ENST00000262482.11	NP_056343.1	Q9H6Y7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF167	ENST00000262482.11 linkuse as main transcript	c.291+7G>A		splice_region_variant, intron_variant		2	NM_015528.3	ENSP00000262482.6		Q9H6Y7-1

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68258

AN:

151794

Hom.:

17060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.486

GnomAD3 exomes

AF:

0.473

AC:

118852

AN:

251056

Hom.:

30695

AF XY:

0.478

AC XY:

64846

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.451

Gnomad ASJ exome

AF:

0.526

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.361

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.546

AC:

797511

AN:

1461568

Hom.:

226233

Cov.:

AF XY:

0.541

AC XY:

393651

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.257

Gnomad4 AMR exome

AF:

0.450

Gnomad4 ASJ exome

AF:

0.529

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.367

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.592

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.450

AC:

68300

AN:

151912

Hom.:

17069

Cov.:

AF XY:

0.440

AC XY:

32677

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.268

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.517

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.489

Alfa

AF:

0.553

Hom.:

30005

Bravo

AF:

0.441

Asia WGS

AF:

0.262

AC:

912

AN:

3478

EpiCase

AF:

0.574

EpiControl

AF:

0.576

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Apr 20, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0068

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