22-43113840-G-C

Position:

• chr22-43113840-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BIK	NM_001197.5	c.-8+3037G>C		intron_variant		ENST00000216115.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIK	ENST00000216115.3	c.-8+3037G>C		intron_variant		1	NM_001197.5	P1

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

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.173

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1883264; hg19: chr22-43509846;