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GeneBe

22-23181270-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004327.4(BCR):c.310G>A(p.Gly104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 150,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BCR
NM_004327.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0970
Variant links:
Genes affected
BCR (HGNC:1014): (BCR activator of RhoGEF and GTPase) A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07980487).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCRNM_004327.4 linkuse as main transcriptc.310G>A p.Gly104Arg missense_variant 1/23 ENST00000305877.13
BCRNM_021574.3 linkuse as main transcriptc.310G>A p.Gly104Arg missense_variant 1/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCRENST00000305877.13 linkuse as main transcriptc.310G>A p.Gly104Arg missense_variant 1/231 NM_004327.4 P1P11274-1
BCRENST00000359540.7 linkuse as main transcriptc.310G>A p.Gly104Arg missense_variant 1/221 P11274-2
BCRENST00000479188.5 linkuse as main transcriptn.129+1438G>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00000665
AC:
1
AN:
150284
Hom.:
0
Cov.:
32
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1112090
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
533178
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:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000665
AC:
1
AN:
150284
Hom.:
0
Cov.:
32
AF XY:
0.0000136
AC XY:
1
AN XY:
73336
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:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 GeneticsAug 03, 2022The c.310G>A (p.G104R) alteration is located in exon 1 (coding exon 1) of the BCR gene. This alteration results from a G to A substitution at nucleotide position 310, causing the glycine (G) at amino acid position 104 to be replaced by an arginine (R). 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
Benign
0.15
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
Cadd
Benign
16
Dann
Uncertain
0.99
DEOGEN2
Benign
0.30
T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.077
N
LIST_S2
Benign
0.81
T;T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.080
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.7
N;N
REVEL
Benign
0.022
Sift
Benign
0.11
T;T
Sift4G
Benign
0.29
T;T
Polyphen
0.0010
B;B
Vest4
0.055
MutPred
0.19
Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);
MVP
0.24
MPC
1.3
ClinPred
0.070
T
GERP RS
0.38
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.055
gMVP
0.24

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: rs944890390; hg19: chr22-23523457; API