2-111168355-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_138621.5(BCL2L11):​c.*4124C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00481 in 152,298 control chromosomes in the GnomAD database, including 2 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 0.0048 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BCL2L11
NM_138621.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.08
Variant links:
Genes affected
BCL2L11 (HGNC:994): (BCL2 like 11) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]
MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00481 (732/152298) while in subpopulation AFR AF= 0.0163 (677/41562). AF 95% confidence interval is 0.0153. There are 2 homozygotes in gnomad4. There are 358 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 732 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BCL2L11NM_138621.5 linkuse as main transcriptc.*4124C>T 3_prime_UTR_variant 4/4 ENST00000393256.8 NP_619527.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BCL2L11ENST00000393256.8 linkuse as main transcriptc.*4124C>T 3_prime_UTR_variant 4/41 NM_138621.5 ENSP00000376943 P1O43521-1
MIR4435-2HGENST00000645030.2 linkuse as main transcriptn.453-131433G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00480
AC:
731
AN:
152180
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0163
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00281
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00430
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
434
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
262
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00481
AC:
732
AN:
152298
Hom.:
2
Cov.:
33
AF XY:
0.00481
AC XY:
358
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0163
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00353
Hom.:
0
Bravo
AF:
0.00556
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
21
DANN
Benign
0.68
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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

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

Other links and lift over

dbSNP: rs73954984; hg19: chr2-111925932; API