chr3-107747993-C-T

Variant names:

• chr3-107747993-C-T
• rs150121801
• NM_001142568.3:c.779C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001142568.3(BBX):​c.779C>T​(p.Ala260Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,613,314 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (26 hom.)
• Consequence: BBX NM_001142568.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.460
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003517747).
• BP6: Variant 3-107747993-C-T is Benign according to our data. Variant chr3-107747993-C-T is described in ClinVar as Benign. ClinVar VariationId is 773704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 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.779C>T	p.Ala260Val	missense	Exon 9 of 18	NP_001136040.1	Q8WY36-1
	BBX	NM_020235.7		c.779C>T	p.Ala260Val	missense	Exon 9 of 17	NP_064620.2
	BBX	NM_001276286.2		c.779C>T	p.Ala260Val	missense	Exon 9 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.779C>T	p.Ala260Val	missense	Exon 9 of 18	ENSP00000319974.8	Q8WY36-1
	BBX	ENST00000415149.6	TSL:1	c.779C>T	p.Ala260Val	missense	Exon 9 of 17	ENSP00000408358.2	Q8WY36-2
	BBX	ENST00000416476.6	TSL:1	c.779C>T	p.Ala260Val	missense	Exon 9 of 17	ENSP00000403860.2	Q8WY36-3

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 165 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00242 AC: 606 AN: 250584 AF XY: 0.00306

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000901

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.00168

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00190 AC: 2777 AN: 1461036 Hom.: 26 Cov.: 30 AF XY: 0.00219 AC XY: 1592 AN XY: 726830

African (AFR) AF: 0.0000897 AC: 3 AN: 33434

American (AMR) AF: 0.000918 AC: 41 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00237 AC: 62 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39624

South Asian (SAS) AF: 0.0112 AC: 967 AN: 86142

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53372

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5756

European-Non Finnish (NFE) AF: 0.00135 AC: 1502 AN: 1111576

Other (OTH) AF: 0.00249 AC: 150 AN: 60360

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152278 Hom.: 2 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74442

African (AFR) AF: 0.000120 AC: 5 AN: 41562

American (AMR) AF: 0.000785 AC: 12 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00974 AC: 47 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00122 AC: 83 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00136 Hom.: 2

Bravo AF: 0.000895

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.00261 AC: 317

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00197

EpiControl AF: 0.00244

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	9.7
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0035	T
MetaSVM	Uncertain	0.70	D
MutationAssessor	Benign	0.34	N
PhyloP100		0.46
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.27
Sift	Benign	0.28	T
Sift4G	Benign	0.36	T
Polyphen		0.050	B
Vest4		0.11
MVP		0.69
MPC		0.15
ClinPred		0.011	T
GERP RS		0.99
Varity_R		0.030
gMVP		0.19
Mutation Taster		=99/1	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: rs150121801; hg19: chr3-107466840;