dbSNP rs1161022457: BTRC:c.49-6C>G (chr10-101430339-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_033637.4(BTRC):c.49-6C>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000686 in 1,456,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BTRC
NM_033637.4 splice_region, intron

Scores

Splicing: ADA: 0.6976

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.75

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.18).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033637.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BTRC	NM_033637.4	MANE Select	c.49-6C>G	splice_region intron	N/A	NP_378663.1	Q9Y297-1
BTRC	NM_001256856.2		c.49-6C>G	splice_region intron	N/A	NP_001243785.1	B7Z3H4
BTRC	NM_003939.5		c.49-31642C>G	intron	N/A	NP_003930.1	Q9Y297-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BTRC	ENST00000370187.8	TSL:1 MANE Select	c.49-6C>G	splice_region intron	N/A	ENSP00000359206.3	Q9Y297-1
BTRC	ENST00000393441.8	TSL:1	c.49-6C>G	splice_region intron	N/A	ENSP00000377088.5	B7Z3H4
BTRC	ENST00000408038.6	TSL:1	c.49-31642C>G	intron	N/A	ENSP00000385339.2	Q9Y297-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249522

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456982

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33342

American (AMR)

AF:

0.00

AC:

AN:

44462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.00

AC:

AN:

85888

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108250

Other (OTH)

AF:

0.00

AC:

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

5.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.70

dbscSNV1_RF

Benign

0.50

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over