NM_033637.4:c.*840_*848delAACAGTGGA

Variant names:

• chr10-101553962-CAACAGTGGA-C
• rs16405
• NM_033637.4:c.*840_*848delAACAGTGGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_033637.4(BTRC):​c.*840_*848delAACAGTGGA 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
• Publications: 12 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 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.*840_*848delAACAGTGGA		3_prime_UTR	Exon 15 of 15	NP_378663.1
	BTRC	NM_001256856.2		c.*840_*848delAACAGTGGA		3_prime_UTR	Exon 14 of 14	NP_001243785.1
	BTRC	NM_003939.5		c.*840_*848delAACAGTGGA		3_prime_UTR	Exon 14 of 14	NP_003930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTRC	ENST00000370187.8	TSL:1 MANE Select	c.*840_*848delAACAGTGGA		3_prime_UTR	Exon 15 of 15	ENSP00000359206.3
	BTRC	ENST00000393441.8	TSL:1	c.*840_*848delAACAGTGGA		3_prime_UTR	Exon 14 of 14	ENSP00000377088.5
	BTRC	ENST00000408038.6	TSL:1	c.*840_*848delAACAGTGGA		3_prime_UTR	Exon 14 of 14	ENSP00000385339.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.200 AC: 52 AN: 260

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 4 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.541 AC: 22325 AN: 41290

American (AMR) AF: 0.287 AC: 4383 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.659 AC: 3378 AN: 5124

South Asian (SAS) AF: 0.328 AC: 1581 AN: 4818

European-Finnish (FIN) AF: 0.206 AC: 2178 AN: 10566

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12690 AN: 67976

Other (OTH) AF: 0.306 AC: 644 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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