rs16405

chr10-101553962-CAACAGTGGA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_033637.4(BTRC):c.*840_*848del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,084 control chromosomes in the GnomAD database, including 9,719 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (9714 hom., cov: 0)
  • Exomes 𝑓: 0.20 (5 hom.)
• Consequence: BTRC NM_033637.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTRC	NM_033637.4	c.*840_*848del		3_prime_UTR_variant	15/15	ENST00000370187.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTRC	ENST00000370187.8	c.*840_*848del		3_prime_UTR_variant	15/15	1	NM_033637.4	A1
BTRC	ENST00000393441.8	c.*840_*848del		3_prime_UTR_variant	14/14	1
BTRC	ENST00000408038.6	c.*840_*848del		3_prime_UTR_variant	14/14	1		P4

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47959 AN: 151688 Hom.: 9703 Cov.: 0

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.203 AC: 56 AN: 276 Hom.: 5 AF XY: 0.215 AC XY: 37 AN XY: 172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.316 AC: 48008 AN: 151808 Hom.: 9714 Cov.: 0 AF XY: 0.317 AC XY: 23547 AN XY: 74200

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.306

Alfa AF: 0.258 Hom.: 781

Bravo AF: 0.333

Asia WGS AF: 0.456 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16405; hg19: chr10-103313719; COSMIC: COSV64579552; COSMIC: COSV64579552;