rs2049339

Positions:

• chr3-107752852-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142568.3(BBX):​c.826-2746T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,180 control chromosomes in the GnomAD database, including 1,852 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1852 hom., cov: 32)
• Consequence: BBX NM_001142568.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBX	NM_001142568.3	c.826-2746T>G		intron_variant		ENST00000325805.13	NP_001136040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBX	ENST00000325805.13	c.826-2746T>G		intron_variant		1	NM_001142568.3	ENSP00000319974	P4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21130 AN: 152060 Hom.: 1852 Cov.: 32

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.139 AC: 21120 AN: 152180 Hom.: 1852 Cov.: 32 AF XY: 0.138 AC XY: 10234 AN XY: 74396

Gnomad4 AFR AF: 0.0449

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0282

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.147

Alfa AF: 0.191 Hom.: 5955

Bravo AF: 0.130

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs2049339; hg19: chr3-107471699;