rs17767748

chr10-101526143-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.960

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]

ACMG classification

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	UniProt
BTRC	NM_033637.4	c.687C>T	p.Ile229=	synonymous_variant	6/15	ENST00000370187.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10111 AN: 152010 Hom.: 351 Cov.: 32

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

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.: 31 AF XY: 0.0700 AC XY: 50925 AN XY: 727218

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.: 32 AF XY: 0.0648 AC XY: 4822 AN XY: 74368

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

BTRC-related disorder Benign:1

Benign, criteria provided, single submitter

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

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

Other links and lift over

dbSNP: rs17767748; hg19: chr10-103285900; COSMIC: COSV64561244; COSMIC: COSV64561244;