rs12479254

Variant names:

• chr2-241563541-C-T
• rs12479254
• NM_032515.5:c.349+1065C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BOK	NM_032515.5	c.349+1065C>T		intron_variant	Intron 3 of 4	ENST00000318407.5	NP_115904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BOK	ENST00000318407.5	c.349+1065C>T		intron_variant	Intron 3 of 4	1	NM_032515.5	ENSP00000314132.3

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

African (AFR) AF: 0.699 AC: 28974 AN: 41476

American (AMR) AF: 0.713 AC: 10906 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2432 AN: 3468

East Asian (EAS) AF: 0.678 AC: 3490 AN: 5144

South Asian (SAS) AF: 0.670 AC: 3228 AN: 4820

European-Finnish (FIN) AF: 0.616 AC: 6512 AN: 10578

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40479 AN: 67956

Other (OTH) AF: 0.671 AC: 1418 AN: 2114

Alfa AF: 0.610 Hom.: 47235

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
PhyloP100		-1.7
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: rs12479254; hg19: chr2-242502956;