22-43129250-T-G

Variant names:

• chr22-43129250-T-G
• rs145876995
• NM_001197.5:c.428T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001197.5(BIK):​c.428T>G​(p.Leu143Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: BIK NM_001197.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33118218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIK	NM_001197.5	c.428T>G	p.Leu143Arg	missense_variant	Exon 5 of 5	ENST00000216115.3	NP_001188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIK	ENST00000216115.3	c.428T>G	p.Leu143Arg	missense_variant	Exon 5 of 5	1	NM_001197.5	ENSP00000216115.2

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150800 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150800 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73692

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.12
Sift	Benign	0.20	T
Sift4G	Uncertain	0.019	D
Polyphen		0.98	D
Vest4		0.37
MutPred		0.55		Gain of methylation at L143 (P = 0.0346);
MVP		0.51
MPC		0.033
ClinPred		0.58	D
GERP RS		-0.50
Varity_R		0.19
gMVP		0.049

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: rs145876995; hg19: chr22-43525256;