NM_001142568.3:c.906+5229T>G

Variant names:

• chr3-107760907-T-G
• rs1403774
• NM_001142568.3:c.906+5229T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142568.3(BBX):​c.906+5229T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,014 control chromosomes in the GnomAD database, including 10,911 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 0.36 (10911 hom., cov: 31)
• Consequence: BBX NM_001142568.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBX	NM_001142568.3	MANE Select	c.906+5229T>G		intron	N/A	NP_001136040.1
	BBX	NM_020235.7		c.906+5229T>G		intron	N/A	NP_064620.2
	BBX	NM_001276286.2		c.906+5229T>G		intron	N/A	NP_001263215.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBX	ENST00000325805.13	TSL:1 MANE Select	c.906+5229T>G		intron	N/A	ENSP00000319974.8
	BBX	ENST00000415149.6	TSL:1	c.906+5229T>G		intron	N/A	ENSP00000408358.2
	BBX	ENST00000416476.6	TSL:1	c.906+5229T>G		intron	N/A	ENSP00000403860.2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54368 AN: 151896 Hom.: 10888 Cov.: 31

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.358 AC: 54418 AN: 152014 Hom.: 10911 Cov.: 31 AF XY: 0.364 AC XY: 27050 AN XY: 74292

African (AFR) AF: 0.265 AC: 10992 AN: 41476

American (AMR) AF: 0.398 AC: 6074 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3466

East Asian (EAS) AF: 0.922 AC: 4757 AN: 5158

South Asian (SAS) AF: 0.378 AC: 1818 AN: 4806

European-Finnish (FIN) AF: 0.422 AC: 4459 AN: 10570

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23823 AN: 67960

Other (OTH) AF: 0.359 AC: 758 AN: 2114

Alfa AF: 0.338 Hom.: 15027

Bravo AF: 0.358

Asia WGS AF: 0.631 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.65
PhyloP100		0.30
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: rs1403774; hg19: chr3-107479754;