rs17767748

Variant names:

• chr10-101526143-C-T
• rs17767748
• NM_033637.4:c.687C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101526143-C-T
• chr10-101526143-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033637.4(BTRC):​c.687C>T​(p.Ile229Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,613,960 control chromosomes in the GnomAD database, including 4,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (353 hom., cov: 32)
  • Exomes 𝑓: 0.071 (3885 hom.)
• Consequence: BTRC NM_033637.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.960
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 10-101526143-C-T is Benign according to our data. Variant chr10-101526143-C-T is described in ClinVar as Benign. ClinVar VariationId is 1658891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 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.687C>T	p.Ile229Ile	synonymous	Exon 6 of 15	NP_378663.1	Q9Y297-1
	BTRC	NM_001256856.2		c.609C>T	p.Ile203Ile	synonymous	Exon 5 of 14	NP_001243785.1	B7Z3H4
	BTRC	NM_003939.5		c.579C>T	p.Ile193Ile	synonymous	Exon 5 of 14	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.687C>T	p.Ile229Ile	synonymous	Exon 6 of 15	ENSP00000359206.3	Q9Y297-1
	BTRC	ENST00000393441.8	TSL:1	c.609C>T	p.Ile203Ile	synonymous	Exon 5 of 14	ENSP00000377088.5	B7Z3H4
	BTRC	ENST00000408038.6	TSL:1	c.579C>T	p.Ile193Ile	synonymous	Exon 5 of 14	ENSP00000385339.2	Q9Y297-2

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10111 AN: 152010 Hom.: 351 Cov.: 32

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0527

GnomAD2 exomes AF: 0.0566 AC: 14238 AN: 251456 AF XY: 0.0568

Gnomad AFR exome AF: 0.0675

Gnomad AMR exome AF: 0.0466

Gnomad ASJ exome AF: 0.0468

Gnomad EAS exome AF: 0.00120

Gnomad FIN exome AF: 0.0583

Gnomad NFE exome AF: 0.0714

Gnomad OTH exome AF: 0.0590

GnomAD4 exome AF: 0.0707 AC: 103344 AN: 1461832 Hom.: 3885 Cov.: 31 AF XY: 0.0700 AC XY: 50925 AN XY: 727218

African (AFR) AF: 0.0689 AC: 2305 AN: 33478

American (AMR) AF: 0.0465 AC: 2078 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0503 AC: 1315 AN: 26134

East Asian (EAS) AF: 0.000806 AC: 32 AN: 39698

South Asian (SAS) AF: 0.0422 AC: 3642 AN: 86252

European-Finnish (FIN) AF: 0.0631 AC: 3370 AN: 53420

Middle Eastern (MID) AF: 0.0286 AC: 165 AN: 5768

European-Non Finnish (NFE) AF: 0.0779 AC: 86673 AN: 1111964

Other (OTH) AF: 0.0623 AC: 3764 AN: 60396

GnomAD4 genome AF: 0.0666 AC: 10126 AN: 152128 Hom.: 353 Cov.: 32 AF XY: 0.0648 AC XY: 4822 AN XY: 74368

African (AFR) AF: 0.0702 AC: 2914 AN: 41500

American (AMR) AF: 0.0590 AC: 902 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 175 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5184

South Asian (SAS) AF: 0.0400 AC: 192 AN: 4804

European-Finnish (FIN) AF: 0.0583 AC: 617 AN: 10582

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0741 AC: 5040 AN: 67992

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0677 Hom.: 667

Bravo AF: 0.0660

Asia WGS AF: 0.0410 AC: 145 AN: 3478

EpiCase AF: 0.0700

EpiControl AF: 0.0676

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	BTRC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.7
DANN	Benign	0.69
PhyloP100		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs17767748; hg19: chr10-103285900; COSMIC: COSV64561244; COSMIC: COSV64561244;