rs3127234

Positions:

• chr10-101544355-G-A
• chr10-101544355-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033637.4(BTRC):​c.1656+5984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,310 control chromosomes in the GnomAD database, including 31,512 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31512 hom., cov: 30)
• Consequence: BTRC NM_033637.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTRC	NM_033637.4	c.1656+5984G>A		intron_variant		ENST00000370187.8	NP_378663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTRC	ENST00000370187.8	c.1656+5984G>A		intron_variant		1	NM_033637.4	ENSP00000359206.3
BTRC	ENST00000393441.8	c.1578+5984G>A		intron_variant		1		ENSP00000377088.5
BTRC	ENST00000408038.6	c.1548+5984G>A		intron_variant		1		ENSP00000385339.2
BTRC	ENST00000493877.1	n.279+5984G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95696 AN: 151198 Hom.: 31465 Cov.: 30

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.618

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.633 AC: 95801 AN: 151310 Hom.: 31512 Cov.: 30 AF XY: 0.639 AC XY: 47185 AN XY: 73842

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.615

Alfa AF: 0.579 Hom.: 4306

Bravo AF: 0.639

Asia WGS AF: 0.795 AC: 2762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.52

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: rs3127234; hg19: chr10-103304112;