22-43122269-A-G

Position:

• chr22-43122269-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	UniProt
BIK	NM_001197.5	c.-7-1747A>G		intron_variant		ENST00000216115.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIK	ENST00000216115.3	c.-7-1747A>G		intron_variant		1	NM_001197.5	P1

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

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.836

Alfa AF: 0.871 Hom.: 91083

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

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: rs742134; hg19: chr22-43518275;