22-43117150-T-C

Position:

• chr22-43117150-T-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+6347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,056 control chromosomes in the GnomAD database, including 56,808 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 (56808 hom., cov: 30)
• Consequence: BIK NM_001197.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIK	NM_001197.5	c.-8+6347T>C		intron_variant		ENST00000216115.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIK	ENST00000216115.3	c.-8+6347T>C		intron_variant		1	NM_001197.5	P1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131203 AN: 151938 Hom.: 56753 Cov.: 30

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.864 AC: 131320 AN: 152056 Hom.: 56808 Cov.: 30 AF XY: 0.865 AC XY: 64281 AN XY: 74310

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.903

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.845

Alfa AF: 0.875 Hom.: 14601

Bravo AF: 0.858

Asia WGS AF: 0.893 AC: 3106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.17

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: rs5751435; hg19: chr22-43513156;