22-43122269-A-G

Variant names:

• chr22-43122269-A-G
• rs742134
• NM_001197.5:c.-7-1747A>G

Variant summary

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

The NM_001197.5(BIK):​c.-7-1747A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,230 control chromosomes in the GnomAD database, including 55,901 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 (55901 hom., cov: 33)
• Consequence: BIK NM_001197.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 41 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIK	NM_001197.5	c.-7-1747A>G		intron_variant	Intron 1 of 4	ENST00000216115.3	NP_001188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIK	ENST00000216115.3	c.-7-1747A>G		intron_variant	Intron 1 of 4	1	NM_001197.5	ENSP00000216115.2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130167 AN: 152112 Hom.: 55857 Cov.: 33

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.856 AC: 130272 AN: 152230 Hom.: 55901 Cov.: 33 AF XY: 0.858 AC XY: 63856 AN XY: 74438

African (AFR) AF: 0.825 AC: 34253 AN: 41526

American (AMR) AF: 0.810 AC: 12374 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2768 AN: 3472

East Asian (EAS) AF: 0.952 AC: 4930 AN: 5180

South Asian (SAS) AF: 0.877 AC: 4230 AN: 4824

European-Finnish (FIN) AF: 0.908 AC: 9629 AN: 10608

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59262 AN: 68022

Other (OTH) AF: 0.836 AC: 1765 AN: 2110

Alfa AF: 0.869 Hom.: 153329

Bravo AF: 0.849

Asia WGS AF: 0.893 AC: 3103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.44
PhyloP100		-1.2
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: rs742134; hg19: chr22-43518275;