22-43124107-G-C

Variant names:

• chr22-43124107-G-C
• rs748570562
• NM_001197.5:c.85G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001197.5(BIK):​c.85G>C​(p.Val29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V29F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BIK NM_001197.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048047543).

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.85G>C	p.Val29Leu	missense	Exon 2 of 5	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.85G>C	p.Val29Leu	missense	Exon 2 of 5	ENSP00000216115.2	Q13323
	BIK	ENST00000918052.1		c.85G>C	p.Val29Leu	missense	Exon 2 of 6	ENSP00000588111.1
	BIK	ENST00000910665.1		c.85G>C	p.Val29Leu	missense	Exon 4 of 7	ENSP00000580724.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.043
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.042
Sift	Benign	0.25	T
Sift4G	Benign	0.31	T
Polyphen		0.11	B
Vest4		0.045
MutPred		0.19		Loss of sheet (P = 0.0126)
MVP		0.081
MPC		0.082
ClinPred		0.082	T
GERP RS		-2.7
Varity_R		0.064
gMVP		0.022
Mutation Taster		=99/1	polymorphism

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: rs748570562; hg19: chr22-43520113;