22-43113662-A-G

Variant names:

• chr22-43113662-A-G
• rs9620115
• NM_001197.5:c.-8+2859A>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.-8+2859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,066 control chromosomes in the GnomAD database, including 2,775 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 0.18 (2775 hom., cov: 32)
• Consequence: BIK NM_001197.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 11 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 (AFR) allele frequency at 95% confidence interval = 0.276 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIK	NM_001197.5	MANE Select	c.-8+2859A>G		intron	N/A	NP_001188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIK	ENST00000216115.3	TSL:1 MANE Select	c.-8+2859A>G		intron	N/A	ENSP00000216115.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27095 AN: 151950 Hom.: 2771 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.178 AC: 27120 AN: 152066 Hom.: 2775 Cov.: 32 AF XY: 0.176 AC XY: 13089 AN XY: 74338

African (AFR) AF: 0.280 AC: 11608 AN: 41448

American (AMR) AF: 0.127 AC: 1944 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3468

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5184

South Asian (SAS) AF: 0.121 AC: 584 AN: 4816

European-Finnish (FIN) AF: 0.133 AC: 1400 AN: 10564

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10610 AN: 67990

Other (OTH) AF: 0.175 AC: 370 AN: 2116

Alfa AF: 0.155 Hom.: 4334

Bravo AF: 0.183

Asia WGS AF: 0.0940 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.5
DANN	Benign	0.51
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs9620115; hg19: chr22-43509668;