rs6437740

Variant names:

• chr3-107746970-T-C
• rs6437740
• NM_001142568.3:c.751-995T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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 -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 rank	MANE	Protein	UniProt
BBX	NM_001142568.3	c.751-995T>C		intron_variant	Intron 8 of 17	ENST00000325805.13	NP_001136040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBX	ENST00000325805.13	c.751-995T>C		intron_variant	Intron 8 of 17	1	NM_001142568.3	ENSP00000319974.8

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

African (AFR) AF: 0.287 AC: 11911 AN: 41460

American (AMR) AF: 0.255 AC: 3901 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3472

East Asian (EAS) AF: 0.0470 AC: 244 AN: 5188

South Asian (SAS) AF: 0.197 AC: 951 AN: 4822

European-Finnish (FIN) AF: 0.280 AC: 2961 AN: 10578

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16145 AN: 67972

Other (OTH) AF: 0.235 AC: 495 AN: 2110

Alfa AF: 0.237 Hom.: 10549

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
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs6437740; hg19: chr3-107465817;