3-107716624-C-T

Variant names:

• chr3-107716624-C-T
• rs150018279
• NM_001142568.3:c.180C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001142568.3(BBX):​c.180C>T​(p.Ala60Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,613,476 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (12 hom.)
• Consequence: BBX NM_001142568.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.35
• Publications: 0 publications found

Genes affected

BBX (HGNC:14422): (BBX high mobility group box domain containing) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within bone development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 3-107716624-C-T is Benign according to our data. Variant chr3-107716624-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 714946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.35 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142568.3. 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
	BBX	NM_001142568.3	MANE Select	c.180C>T	p.Ala60Ala	synonymous	Exon 5 of 18	NP_001136040.1	Q8WY36-1
	BBX	NM_020235.7		c.180C>T	p.Ala60Ala	synonymous	Exon 5 of 17	NP_064620.2
	BBX	NM_001276286.2		c.180C>T	p.Ala60Ala	synonymous	Exon 5 of 17	NP_001263215.1	Q8WY36-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBX	ENST00000325805.13	TSL:1 MANE Select	c.180C>T	p.Ala60Ala	synonymous	Exon 5 of 18	ENSP00000319974.8	Q8WY36-1
	BBX	ENST00000415149.6	TSL:1	c.180C>T	p.Ala60Ala	synonymous	Exon 5 of 17	ENSP00000408358.2	Q8WY36-2
	BBX	ENST00000416476.6	TSL:1	c.180C>T	p.Ala60Ala	synonymous	Exon 5 of 17	ENSP00000403860.2	Q8WY36-3

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 237 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00291

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00143 AC: 359 AN: 250904 AF XY: 0.00153

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00242

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00263 AC: 3838 AN: 1461352 Hom.: 12 Cov.: 30 AF XY: 0.00252 AC XY: 1832 AN XY: 726968

African (AFR) AF: 0.000389 AC: 13 AN: 33446

American (AMR) AF: 0.000470 AC: 21 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000986 AC: 85 AN: 86234

European-Finnish (FIN) AF: 0.000786 AC: 42 AN: 53410

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5756

European-Non Finnish (NFE) AF: 0.00316 AC: 3511 AN: 1111638

Other (OTH) AF: 0.00239 AC: 144 AN: 60360

GnomAD4 genome AF: 0.00156 AC: 237 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74346

African (AFR) AF: 0.000530 AC: 22 AN: 41522

American (AMR) AF: 0.000655 AC: 10 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4806

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00291 AC: 198 AN: 68004

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00216 Hom.: 0

Bravo AF: 0.00171

EpiCase AF: 0.00306

EpiControl AF: 0.00225

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs150018279; hg19: chr3-107435471;