rs6437740

chr3-107746970-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.751-995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,080 control chromosomes in the GnomAD database, including 4,910 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 (4910 hom., cov: 32)
• Consequence: BBX NM_001142568.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBX	NM_001142568.3	c.751-995T>C		intron_variant		ENST00000325805.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBX	ENST00000325805.13	c.751-995T>C		intron_variant		1	NM_001142568.3	P4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37752 AN: 151962 Hom.: 4904 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0473

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.248 AC: 37773 AN: 152080 Hom.: 4910 Cov.: 32 AF XY: 0.250 AC XY: 18553 AN XY: 74346

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0470

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.235

Alfa AF: 0.232 Hom.: 6609

Bravo AF: 0.247

Asia WGS AF: 0.129 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.9
Dann	Benign	0.63

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: rs6437740; hg19: chr3-107465817;