rs13004470

chr2-241571668-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.514-629C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,224 control chromosomes in the GnomAD database, including 1,958 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 0.15 (1958 hom., cov: 33)
• Consequence: BOK NM_032515.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BOK	NM_032515.5	c.514-629C>T		intron_variant		ENST00000318407.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BOK	ENST00000318407.5	c.514-629C>T		intron_variant		1	NM_032515.5	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23340 AN: 152106 Hom.: 1957 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.0621

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.154 AC: 23367 AN: 152224 Hom.: 1958 Cov.: 33 AF XY: 0.147 AC XY: 10905 AN XY: 74426

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0621

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.167

Alfa AF: 0.156 Hom.: 3121

Bravo AF: 0.162

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.6
Dann	Benign	0.76

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: rs13004470; hg19: chr2-242511083;