rs4151060

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033637.4(BTRC):c.1627G>T(p.Ala543Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,613,758 control chromosomes in the GnomAD database, including 2,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.030 ( 121 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1902 hom. )

Consequence

BTRC
NM_033637.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 9.57

Variant links:

Genes affected

BTRC (HGNC:1144): (beta-transducin repeat containing E3 ubiquitin protein ligase) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class; in addition to an F-box, this protein contains multiple WD-40 repeats. The encoded protein mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B. Alternatively spliced transcript variants have been described. A related pseudogene exists in chromosome 6. [provided by RefSeq, Mar 2012]

BTRC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027300715).

BP6

Variant 10-101538342-G-T is Benign according to our data. Variant chr10-101538342-G-T is described in ClinVar as [Benign]. Clinvar id is 1534223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTRC	NM_033637.4 link	c.1627G>T	p.Ala543Ser	missense_variant	Exon 13 of 15	ENST00000370187.8	NP_378663.1	Q9Y297-1A0A0S2Z4P6B2R8L3Q68DS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BTRC	ENST00000370187.8 link	c.1627G>T	p.Ala543Ser	missense_variant	Exon 13 of 15	1	NM_033637.4	ENSP00000359206.3	Q9Y297-1
BTRC	ENST00000393441.8 link	c.1549G>T	p.Ala517Ser	missense_variant	Exon 12 of 14	1		ENSP00000377088.5	B7Z3H4
BTRC	ENST00000408038.6 link	c.1519G>T	p.Ala507Ser	missense_variant	Exon 12 of 14	1		ENSP00000385339.2	Q9Y297-2
BTRC	ENST00000493877.1 link	n.250G>T		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4611

AN:

152162

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00886

Gnomad AMI

AF:

0.0593

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.0277

GnomAD3 exomes

AF:

0.0294

AC:

7389

AN:

251454

Hom.:

159

AF XY:

0.0297

AC XY:

4039

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00917

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00843

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.0474

Gnomad OTH exome

AF:

0.0339

GnomAD4 exome

AF:

0.0464

AC:

67745

AN:

1461478

Hom.:

1902

Cov.:

AF XY:

0.0450

AC XY:

32708

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.00735

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.00318

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00861

Gnomad4 FIN exome

AF:

0.0294

Gnomad4 NFE exome

AF:

0.0555

Gnomad4 OTH exome

AF:

0.0396

GnomAD4 genome

AF:

0.0303

AC:

4610

AN:

152280

Hom.:

121

Cov.:

AF XY:

0.0288

AC XY:

2146

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00883

Gnomad4 AMR

AF:

0.0252

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.0315

Gnomad4 NFE

AF:

0.0496

Gnomad4 OTH

AF:

0.0274

Alfa

AF:

0.0424

Hom.:

258

Bravo

AF:

0.0295

TwinsUK

AF:

0.0542

AC:

201

ALSPAC

AF:

0.0550

AC:

212

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.0478

AC:

411

ExAC

AF:

0.0286

AC:

3472

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0434

EpiControl

AF:

0.0465

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

BTRC-related disorder

Benign:1

Mar 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.047

.;T;.

Eigen

Benign

-0.013

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.17

.;N;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.25

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.47

.;T;T

Sift4G

Benign

0.75

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.45

MPC

0.53

ClinPred

0.063

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.18

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