rs9875732

chr3-107742884-T-C

Variant summary

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

The NM_001142568.3(BBX):c.670-1746T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,136 control chromosomes in the GnomAD database, including 6,245 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 0.25 (6245 hom., cov: 32)
• Consequence: BBX NM_001142568.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBX	NM_001142568.3	c.670-1746T>C		intron_variant		ENST00000325805.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBX	ENST00000325805.13	c.670-1746T>C		intron_variant		1	NM_001142568.3	P4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38701 AN: 152018 Hom.: 6246 Cov.: 32

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.254 AC: 38688 AN: 152136 Hom.: 6245 Cov.: 32 AF XY: 0.251 AC XY: 18638 AN XY: 74366

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.273

Alfa AF: 0.331 Hom.: 4189

Bravo AF: 0.242

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.8
Dann	Benign	0.61

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: rs9875732; hg19: chr3-107461731;