10-101485604-G-C

Variant names:

• chr10-101485604-G-C
• rs4436485
• NM_033637.4:c.324+6147G>C

Variant summary

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

The NM_033637.4(BTRC):​c.324+6147G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,124 control chromosomes in the GnomAD database, including 7,976 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 0.30 (7976 hom., cov: 32)
• Consequence: BTRC NM_033637.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 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.324+6147G>C		intron	N/A	NP_378663.1	Q9Y297-1
	BTRC	NM_001256856.2		c.246+6147G>C		intron	N/A	NP_001243785.1	B7Z3H4
	BTRC	NM_003939.5		c.216+6147G>C		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.324+6147G>C		intron	N/A	ENSP00000359206.3	Q9Y297-1
	BTRC	ENST00000393441.8	TSL:1	c.246+6147G>C		intron	N/A	ENSP00000377088.5	B7Z3H4
	BTRC	ENST00000408038.6	TSL:1	c.216+6147G>C		intron	N/A	ENSP00000385339.2	Q9Y297-2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45084 AN: 152006 Hom.: 7977 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.296 AC: 45077 AN: 152124 Hom.: 7976 Cov.: 32 AF XY: 0.292 AC XY: 21743 AN XY: 74356

African (AFR) AF: 0.110 AC: 4576 AN: 41514

American (AMR) AF: 0.333 AC: 5094 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3470

East Asian (EAS) AF: 0.149 AC: 770 AN: 5170

South Asian (SAS) AF: 0.230 AC: 1111 AN: 4824

European-Finnish (FIN) AF: 0.342 AC: 3609 AN: 10554

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27154 AN: 67978

Other (OTH) AF: 0.328 AC: 694 AN: 2116

Alfa AF: 0.336 Hom.: 1193

Bravo AF: 0.289

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.31
DANN	Benign	0.46
PhyloP100		-0.34
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: rs4436485; hg19: chr10-103245361;