rs11191017

Variant names:

• chr10-101453807-G-A
• rs11191017
• NM_033637.4:c.157-8174G>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.157-8174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,164 control chromosomes in the GnomAD database, including 1,854 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 0.14 (1854 hom., cov: 32)
• Consequence: BTRC NM_033637.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTRC	NM_033637.4	MANE Select	c.157-8174G>A		intron	N/A	NP_378663.1	Q9Y297-1
	BTRC	NM_001256856.2		c.156+23355G>A		intron	N/A	NP_001243785.1	B7Z3H4
	BTRC	NM_003939.5		c.49-8174G>A		intron	N/A	NP_003930.1	Q9Y297-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTRC	ENST00000370187.8	TSL:1 MANE Select	c.157-8174G>A		intron	N/A	ENSP00000359206.3	Q9Y297-1
	BTRC	ENST00000393441.8	TSL:1	c.156+23355G>A		intron	N/A	ENSP00000377088.5	B7Z3H4
	BTRC	ENST00000408038.6	TSL:1	c.49-8174G>A		intron	N/A	ENSP00000385339.2	Q9Y297-2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20909 AN: 152046 Hom.: 1854 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0369

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.137 AC: 20899 AN: 152164 Hom.: 1854 Cov.: 32 AF XY: 0.135 AC XY: 10064 AN XY: 74376

African (AFR) AF: 0.0426 AC: 1770 AN: 41540

American (AMR) AF: 0.129 AC: 1978 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3466

East Asian (EAS) AF: 0.0370 AC: 192 AN: 5186

South Asian (SAS) AF: 0.0934 AC: 450 AN: 4820

European-Finnish (FIN) AF: 0.181 AC: 1919 AN: 10580

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13420 AN: 67966

Other (OTH) AF: 0.142 AC: 300 AN: 2116

Alfa AF: 0.181 Hom.: 1441

Bravo AF: 0.130

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.33
PhyloP100		0.41
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: rs11191017; hg19: chr10-103213564;