Variant 2-226914283-C-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_001167608.3(RHBDD1):c.788C>T(p.Thr263Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,613,768 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 14 hom. )

Consequence

RHBDD1
NM_001167608.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.00

Variant links:

Genes affected

RHBDD1 (HGNC:23081): (rhomboid domain containing 1) Enables serine-type endopeptidase activity. Involved in several processes, including cellular response to unfolded protein; membrane protein proteolysis; and positive regulation of protein catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

RHBDD1 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=0.006077379).

BP6

Variant 2-226914283-C-T is Benign according to our data. Variant chr2-226914283-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651953.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDD1	NM_001167608.3 linkuse as main transcript	c.788C>T	p.Thr263Met	missense_variant	8/9	ENST00000392062.7	NP_001161080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHBDD1	ENST00000392062.7 linkuse as main transcript	c.788C>T	p.Thr263Met	missense_variant	8/9	5	NM_001167608.3	ENSP00000375914	P1	Q8TEB9-1

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

533

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00631

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00322

AC:

809

AN:

250876

Hom.:

AF XY:

0.00314

AC XY:

425

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00753

Gnomad NFE exome

AF:

0.00503

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00304

AC:

4439

AN:

1461530

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2272

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00367

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00732

Gnomad4 NFE exome

AF:

0.00338

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00350

AC:

533

AN:

152238

Hom.:

Cov.:

AF XY:

0.00341

AC XY:

254

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00661

Gnomad4 NFE

AF:

0.00631

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00473

Hom.:

Bravo

AF:

0.00221

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00341

AC:

414

EpiCase

AF:

0.00382

EpiControl

AF:

0.00249

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

Jan 01, 2023

RHBDD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.2

DANN

Benign

0.95

DEOGEN2

Benign

0.0063

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.25

.;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.78

N;N;N

REVEL

Benign

0.013

Sift

Benign

0.22

T;T;D

Sift4G

Benign

0.10

T;T;T

Polyphen

0.60

P;P;.

Vest4

0.037

MVP

0.14

MPC

0.050

ClinPred

0.0031

GERP RS

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.011

gMVP

0.45

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