Genetic Variant RNF151:c.149+8C>T (chr16-1967427-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_174903.6(RNF151):c.149+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,611,230 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 35 hom. )

Consequence

RNF151
NM_174903.6 splice_region, intron

Scores

Splicing: ADA: 0.00001172

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.929

Variant links:

Genes affected

RNF151 (HGNC:23235): (ring finger protein 151) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RNF151 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 16-1967427-C-T is Benign according to our data. Variant chr16-1967427-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645955.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RNF151	NM_174903.6 link	c.149+8C>T	splice_region_variant, intron_variant	Intron 2 of 3	ENST00000569714.6	NP_777563.2
RNF151	NM_001348711.2 link	c.149+8C>T	splice_region_variant, intron_variant	Intron 2 of 3		NP_001335640.1
RNF151	XM_005255129.5 link	c.176+8C>T	splice_region_variant, intron_variant	Intron 2 of 3		XP_005255186.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF151	ENST00000569714.6 link	c.149+8C>T	splice_region_variant, intron_variant	Intron 2 of 3	1	NM_174903.6	ENSP00000456566.1	Q2KHN1
RNF151	ENST00000321392.4 link	c.146+8C>T	splice_region_variant, intron_variant	Intron 1 of 2	1		ENSP00000325794.3	A0A0C4DFQ4
RNF151	ENST00000569210.6 link	c.149+8C>T	splice_region_variant, intron_variant	Intron 2 of 3	2		ENSP00000454886.1	H3BNJ8

Frequencies

GnomAD3 genomes

AF:

0.00356

AC:

541

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00553

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00388

AC:

947

AN:

244294

Hom.:

AF XY:

0.00417

AC XY:

555

AN XY:

133016

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.000762

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00556

Gnomad FIN exome

AF:

0.00331

Gnomad NFE exome

AF:

0.00484

Gnomad OTH exome

AF:

0.00438

GnomAD4 exome

AF:

0.00483

AC:

7053

AN:

1459040

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

3519

AN XY:

725728

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000629

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00500

Gnomad4 FIN exome

AF:

0.00261

Gnomad4 NFE exome

AF:

0.00522

Gnomad4 OTH exome

AF:

0.00567

GnomAD4 genome

AF:

0.00356

AC:

542

AN:

152190

Hom.:

Cov.:

AF XY:

0.00358

AC XY:

266

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00457

Gnomad4 FIN

AF:

0.00321

Gnomad4 NFE

AF:

0.00554

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00437

Hom.:

Bravo

AF:

0.00311

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RNF151: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

5.4

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.27

Position offset: -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