22-43113840-G-C

Variant names:

• chr22-43113840-G-C
• rs1883264
• NM_001197.5:c.-8+3037G>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+3037G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,106 control chromosomes in the GnomAD database, including 2,918 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 (2918 hom., cov: 32)
• Consequence: BIK NM_001197.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIK	NM_001197.5	c.-8+3037G>C		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.-8+3037G>C		intron_variant	Intron 1 of 4	1	NM_001197.5	ENSP00000216115.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27451 AN: 151988 Hom.: 2915 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.181 AC: 27469 AN: 152106 Hom.: 2918 Cov.: 32 AF XY: 0.178 AC XY: 13228 AN XY: 74374

African (AFR) AF: 0.292 AC: 12123 AN: 41458

American (AMR) AF: 0.125 AC: 1915 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3466

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5182

South Asian (SAS) AF: 0.114 AC: 548 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1400 AN: 10588

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10550 AN: 67998

Other (OTH) AF: 0.173 AC: 364 AN: 2108

Alfa AF: 0.0813 Hom.: 122

Bravo AF: 0.185

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.56
PhyloP100		0.11
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: rs1883264; hg19: chr22-43509846;