Variant 16-58642-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022450.5(RHBDF1):c.2266C>A(p.Leu756Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000871 in 1,613,478 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00089 ( 6 hom. )

Consequence

RHBDF1
NM_022450.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.50

Variant links:

Genes affected

RHBDF1 (HGNC:20561): (rhomboid 5 homolog 1) Predicted to enable growth factor binding activity and serine-type endopeptidase activity. Involved in several processes, including negative regulation of protein secretion; regulation of epidermal growth factor receptor signaling pathway; and regulation of proteasomal protein catabolic process. Located in Golgi membrane and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

RHBDF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009865195).

BP6

Variant 16-58642-G-T is Benign according to our data. Variant chr16-58642-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645766.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDF1	NM_022450.5 linkuse as main transcript	c.2266C>A	p.Leu756Ile	missense_variant	18/18	ENST00000262316.10	NP_071895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RHBDF1	ENST00000262316.10 linkuse as main transcript	c.2266C>A	p.Leu756Ile	missense_variant	18/18	1	NM_022450.5	ENSP00000262316	P1
RHBDF1	ENST00000448893.1 linkuse as main transcript	c.397C>A	p.Leu133Ile	missense_variant	5/5	3		ENSP00000406397
RHBDF1	ENST00000428730.5 linkuse as main transcript	c.*1580C>A		3_prime_UTR_variant, NMD_transcript_variant	17/17	5		ENSP00000411508

Frequencies

GnomAD3 genomes

AF:

0.000716

AC:

109

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00128

AC:

320

AN:

250810

Hom.:

AF XY:

0.00161

AC XY:

218

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00585

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000777

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000887

AC:

1296

AN:

1461112

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

786

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00601

Gnomad4 FIN exome

AF:

0.000417

Gnomad4 NFE exome

AF:

0.000513

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.000715

AC:

109

AN:

152366

Hom.:

Cov.:

AF XY:

0.000859

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00517

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000582

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00137

AC:

166

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00124

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

RHBDF1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

Eigen

Benign

0.025

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0099

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.43

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.97

REVEL

Benign

0.058

Sift

Benign

0.091

Sift4G

Benign

0.26

Polyphen

0.011

Vest4

0.34

MVP

0.39

MPC

0.40

ClinPred

0.015

GERP RS

5.2

Varity_R

0.24

gMVP

0.67

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