22-43117150-T-C

Variant names:

• chr22-43117150-T-C
• rs5751435
• NM_001197.5:c.-8+6347T>C

Variant summary

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

The NM_001197.5(BIK):​c.-8+6347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,056 control chromosomes in the GnomAD database, including 56,808 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 0.86 (56808 hom., cov: 30)
• Consequence: BIK NM_001197.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 7 publications found

Genes affected

BIK (HGNC:1051): (BCL2 interacting killer) The protein encoded by this gene shares a critical BH3 domain with other death-promoting proteins, such as BID, BAK, BAD and BAX, that is required for its pro-apoptotic activity, and for interaction with anti-apoptotic members of the BCL2 family, and viral survival-promoting proteins. Since the activity of this protein is suppressed in the presence of survival-promoting proteins, it is suggested as a likely target for anti-apoptotic proteins. [provided by RefSeq, Sep 2011]

BIK Gene-Disease associations (from GenCC):

• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIK	NM_001197.5	MANE Select	c.-8+6347T>C		intron	N/A	NP_001188.1	Q13323

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIK	ENST00000216115.3	TSL:1 MANE Select	c.-8+6347T>C		intron	N/A	ENSP00000216115.2	Q13323
	BIK	ENST00000918052.1		c.-8+6347T>C		intron	N/A	ENSP00000588111.1
	BIK	ENST00000910665.1		c.-8+2041T>C		intron	N/A	ENSP00000580724.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131203 AN: 151938 Hom.: 56753 Cov.: 30

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.864 AC: 131320 AN: 152056 Hom.: 56808 Cov.: 30 AF XY: 0.865 AC XY: 64281 AN XY: 74310

African (AFR) AF: 0.850 AC: 35270 AN: 41476

American (AMR) AF: 0.811 AC: 12370 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2792 AN: 3470

East Asian (EAS) AF: 0.953 AC: 4909 AN: 5150

South Asian (SAS) AF: 0.877 AC: 4225 AN: 4816

European-Finnish (FIN) AF: 0.903 AC: 9560 AN: 10586

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.873 AC: 59356 AN: 67990

Other (OTH) AF: 0.845 AC: 1779 AN: 2106

Alfa AF: 0.875 Hom.: 14601

Bravo AF: 0.858

Asia WGS AF: 0.893 AC: 3106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.17
PhyloP100		-1.6
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: rs5751435; hg19: chr22-43513156;