10-101526143-C-T

Position:

chr10-101526143-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033637.4(BTRC):c.687C>T(p.Ile229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,613,960 control chromosomes in the GnomAD database, including 4,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 353 hom., cov: 32)

Exomes 𝑓: 0.071 ( 3885 hom. )

Consequence

BTRC
NM_033637.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.960

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-101526143-C-T is Benign according to our data. Variant chr10-101526143-C-T is described in ClinVar as [Benign]. Clinvar id is 1658891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTRC	NM_033637.4 linkuse as main transcript	c.687C>T	p.Ile229=	synonymous_variant	6/15	ENST00000370187.8	NP_378663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTRC	ENST00000370187.8 linkuse as main transcript	c.687C>T	p.Ile229=	synonymous_variant	6/15	1	NM_033637.4	ENSP00000359206	A1	Q9Y297-1
BTRC	ENST00000393441.8 linkuse as main transcript	c.609C>T	p.Ile203=	synonymous_variant	5/14	1		ENSP00000377088
BTRC	ENST00000408038.6 linkuse as main transcript	c.579C>T	p.Ile193=	synonymous_variant	5/14	1		ENSP00000385339	P4	Q9Y297-2
BTRC	ENST00000465182.1 linkuse as main transcript	n.634C>T		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.0665

AC:

10111

AN:

152010

Hom.:

351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.0589

Gnomad ASJ

AF:

0.0505

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0401

Gnomad FIN

AF:

0.0583

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0741

Gnomad OTH

AF:

0.0527

GnomAD3 exomes

AF:

0.0566

AC:

14238

AN:

251456

Hom.:

479

AF XY:

0.0568

AC XY:

7713

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0675

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.0468

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.0422

Gnomad FIN exome

AF:

0.0583

Gnomad NFE exome

AF:

0.0714

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0707

AC:

103344

AN:

1461832

Hom.:

3885

Cov.:

AF XY:

0.0700

AC XY:

50925

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0689

Gnomad4 AMR exome

AF:

0.0465

Gnomad4 ASJ exome

AF:

0.0503

Gnomad4 EAS exome

AF:

0.000806

Gnomad4 SAS exome

AF:

0.0422

Gnomad4 FIN exome

AF:

0.0631

Gnomad4 NFE exome

AF:

0.0779

Gnomad4 OTH exome

AF:

0.0623

GnomAD4 genome

AF:

0.0666

AC:

10126

AN:

152128

Hom.:

353

Cov.:

AF XY:

0.0648

AC XY:

4822

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0702

Gnomad4 AMR

AF:

0.0590

Gnomad4 ASJ

AF:

0.0505

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0400

Gnomad4 FIN

AF:

0.0583

Gnomad4 NFE

AF:

0.0741

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0684

Hom.:

518

Bravo

AF:

0.0660

Asia WGS

AF:

0.0410

AC:

145

AN:

3478

EpiCase

AF:

0.0700

EpiControl

AF:

0.0676

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

BTRC-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 05, 2020

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

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.7

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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