rs10883631

Variant names:

• chr10-101379138-G-A
• rs10883631
• NM_033637.4:c.48+24910G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033637.4(BTRC):​c.48+24910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,020 control chromosomes in the GnomAD database, including 11,002 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 0.36 (11002 hom., cov: 32)
• Consequence: BTRC NM_033637.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTRC	NM_033637.4	MANE Select	c.48+24910G>A		intron	N/A	NP_378663.1
	BTRC	NM_001256856.2		c.48+24910G>A		intron	N/A	NP_001243785.1
	BTRC	NM_003939.5		c.48+24910G>A		intron	N/A	NP_003930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTRC	ENST00000370187.8	TSL:1 MANE Select	c.48+24910G>A		intron	N/A	ENSP00000359206.3
	BTRC	ENST00000393441.8	TSL:1	c.48+24910G>A		intron	N/A	ENSP00000377088.5
	BTRC	ENST00000408038.6	TSL:1	c.48+24910G>A		intron	N/A	ENSP00000385339.2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54867 AN: 151902 Hom.: 10999 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.361 AC: 54887 AN: 152020 Hom.: 11002 Cov.: 32 AF XY: 0.356 AC XY: 26448 AN XY: 74288

African (AFR) AF: 0.203 AC: 8441 AN: 41480

American (AMR) AF: 0.392 AC: 5984 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1726 AN: 3470

East Asian (EAS) AF: 0.140 AC: 725 AN: 5168

South Asian (SAS) AF: 0.266 AC: 1284 AN: 4822

European-Finnish (FIN) AF: 0.389 AC: 4098 AN: 10542

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31213 AN: 67954

Other (OTH) AF: 0.381 AC: 804 AN: 2108

Alfa AF: 0.401 Hom.: 1687

Bravo AF: 0.355

Asia WGS AF: 0.200 AC: 696 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.47
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10883631; hg19: chr10-103138895;