rs12479254

Positions:

• chr2-241563541-C-T

Variant summary

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

The NM_032515.5(BOK):​c.349+1065C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,054 control chromosomes in the GnomAD database, including 31,842 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 0.65 (31842 hom., cov: 33)
• Consequence: BOK NM_032515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

BOK (HGNC:1087): (BCL2 family apoptosis regulator BOK) The protein encoded by this gene belongs to the BCL2 family, members of which form homo- or heterodimers, and act as anti- or proapoptotic regulators that are involved in a wide variety of cellular processes. Studies in rat show that this protein has restricted expression in reproductive tissues, interacts strongly with some antiapoptotic BCL2 proteins, not at all with proapoptotic BCL2 proteins, and induces apoptosis in transfected cells. Thus, this protein represents a proapoptotic member of the BCL2 family. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BOK	NM_032515.5	c.349+1065C>T		intron_variant		ENST00000318407.5	NP_115904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BOK	ENST00000318407.5	c.349+1065C>T		intron_variant		1	NM_032515.5	ENSP00000314132	P1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98120 AN: 151934 Hom.: 31818 Cov.: 33

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.646 AC: 98198 AN: 152054 Hom.: 31842 Cov.: 33 AF XY: 0.650 AC XY: 48289 AN XY: 74342

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.671

Alfa AF: 0.611 Hom.: 34460

Bravo AF: 0.653

Asia WGS AF: 0.688 AC: 2392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.37

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: rs12479254; hg19: chr2-242502956;