rs9420822

Variant names:

• chr10-101467046-C-A
• rs9420822
• NM_033637.4:c.234+4988C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_033637.4(BTRC):​c.234+4988C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,872 control chromosomes in the GnomAD database, including 11,581 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 0.37 (11581 hom., cov: 31)
• Consequence: BTRC NM_033637.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 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.234+4988C>A		intron	N/A	NP_378663.1	Q9Y297-1
	BTRC	NM_001256856.2		c.157-12322C>A		intron	N/A	NP_001243785.1	B7Z3H4
	BTRC	NM_003939.5		c.126+4988C>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.234+4988C>A		intron	N/A	ENSP00000359206.3	Q9Y297-1
	BTRC	ENST00000393441.8	TSL:1	c.157-12322C>A		intron	N/A	ENSP00000377088.5	B7Z3H4
	BTRC	ENST00000408038.6	TSL:1	c.126+4988C>A		intron	N/A	ENSP00000385339.2	Q9Y297-2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56216 AN: 151754 Hom.: 11578 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.370 AC: 56236 AN: 151872 Hom.: 11581 Cov.: 31 AF XY: 0.365 AC XY: 27065 AN XY: 74226

African (AFR) AF: 0.206 AC: 8525 AN: 41416

American (AMR) AF: 0.395 AC: 6033 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3470

East Asian (EAS) AF: 0.151 AC: 779 AN: 5164

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4822

European-Finnish (FIN) AF: 0.401 AC: 4207 AN: 10502

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32166 AN: 67916

Other (OTH) AF: 0.390 AC: 821 AN: 2106

Alfa AF: 0.412 Hom.: 1789

Bravo AF: 0.364

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		1.9
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: rs9420822; hg19: chr10-103226803;