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GeneBe

7-73539906-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001707.4(BCL7B):c.412A>G(p.Thr138Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,606 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

BCL7B
NM_001707.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.64
Variant links:
Genes affected
BCL7B (HGNC:1005): (BAF chromatin remodeling complex subunit BCL7B) This gene encodes a member of the BCL7 family including BCL7A, BCL7B and BCL7C proteins. This member is BCL7B, which contains a region that is highly similar to the N-terminal segment of BCL7A or BCL7C proteins. The BCL7A protein is encoded by the gene known to be directly involved in a three-way gene translocation in a Burkitt lymphoma cell line. This gene is located at a chromosomal region commonly deleted in Williams syndrome. This gene is highly conserved from C. elegans to human. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2010]

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ACMG classification

Classification made for transcript

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=0.26688766).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCL7BNM_001707.4 linkuse as main transcriptc.412A>G p.Thr138Ala missense_variant 4/6 ENST00000223368.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCL7BENST00000223368.7 linkuse as main transcriptc.412A>G p.Thr138Ala missense_variant 4/61 NM_001707.4 P1Q9BQE9-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152022
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000558
AC:
14
AN:
250846
Hom.:
0
AF XY:
0.0000737
AC XY:
10
AN XY:
135620
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000970
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000458
AC:
67
AN:
1461584
Hom.:
0
Cov.:
30
AF XY:
0.0000413
AC XY:
30
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000522
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152022
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74256
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

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 GeneticsOct 05, 2022The c.412A>G (p.T138A) alteration is located in exon 4 (coding exon 4) of the BCL7B gene. This alteration results from a A to G substitution at nucleotide position 412, causing the threonine (T) at amino acid position 138 to be replaced by an alanine (A). 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
-0.27
T
BayesDel_noAF
Benign
-0.42
Cadd
Pathogenic
26
Dann
Uncertain
0.99
DEOGEN2
Benign
0.080
T;T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.4
N;.
REVEL
Benign
0.15
Sift
Benign
0.65
T;.
Sift4G
Benign
0.66
T;T
Polyphen
0.93
P;.
Vest4
0.36
MVP
0.47
MPC
1.4
ClinPred
0.32
T
GERP RS
5.6
Varity_R
0.11
gMVP
0.065

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: rs369402294; hg19: chr7-72954236; API