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GeneBe

22-17738093-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001196.4(BID):c.500T>C(p.Leu167Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

BID
NM_001196.4 missense

Scores

4
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61
Variant links:
Genes affected
BID (HGNC:1050): (BH3 interacting domain death agonist) This gene encodes a death agonist that heterodimerizes with either agonist BAX or antagonist BCL2, and thus regulate apoptosis. The encoded protein is a member of the BCL-2 family of cell death regulators. It is a mediator of mitochondrial damage induced by caspase-8 (CASP8); CASP8 cleaves this encoded protein, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Aug 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIDNM_001196.4 linkuse as main transcriptc.500T>C p.Leu167Pro missense_variant 5/6 ENST00000622694.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIDENST00000622694.5 linkuse as main transcriptc.500T>C p.Leu167Pro missense_variant 5/61 NM_001196.4 P1P55957-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152200
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251492
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.0000275
AC XY:
20
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000187
Gnomad4 NFE exome
AF:
0.0000270
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152200
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000100
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 03, 2022The c.638T>C (p.L213P) alteration is located in exon 5 (coding exon 5) of the BID gene. This alteration results from a T to C substitution at nucleotide position 638, causing the leucine (L) at amino acid position 213 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
0.13
Cadd
Benign
23
Dann
Uncertain
1.0
Eigen
Uncertain
0.33
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.72
T;.;T;.;T;.;.;.;.
M_CAP
Benign
0.051
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.59
T
MutationTaster
Benign
0.54
D;D;N;N;N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-6.4
D;.;.;.;D;D;D;D;.
REVEL
Uncertain
0.45
Sift
Uncertain
0.0010
D;.;.;.;D;D;D;D;.
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;D;.;.;D;.;D;.
Vest4
0.95
MutPred
0.95
.;.;Gain of disorder (P = 0.0148);.;.;Gain of disorder (P = 0.0148);.;Gain of disorder (P = 0.0148);.;
MVP
0.42
MPC
0.90
ClinPred
0.67
D
GERP RS
4.8
Varity_R
0.92
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778228540; hg19: chr22-18220859; API