Genetic Variant BCL7C:p.Glu179Lys (chr16-30887984-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004765.4(BCL7C):c.535G>A(p.Glu179Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000243 in 1,605,142 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

BCL7C
NM_004765.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

BCL7C (HGNC:1006): (BAF chromatin remodeling complex subunit BCL7C) This gene is identified by the similarity of its product to the N-terminal region of BCL7A protein. 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. The function of this gene has not yet been determined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

BCL7C links:

MIR762HG (HGNC:51386): (MIR762 host gene)

MIR762HG links:

ENSG00000262721 (HGNC:):

ENSG00000262721 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL7C	NM_004765.4 link	c.535G>A	p.Glu179Lys	missense_variant	Exon 6 of 6	ENST00000215115.5	NP_004756.2	Q8WUZ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL7C	ENST00000215115.5 link	c.535G>A	p.Glu179Lys	missense_variant	Exon 6 of 6	1	NM_004765.4	ENSP00000215115.4		Q8WUZ0-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000580

AC:

AN:

241246

Hom.:

AF XY:

0.0000611

AC XY:

AN XY:

130874

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000309

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000409

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000248

AC:

AN:

1453154

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

722840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000353

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.0000725

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.535G>A (p.E179K) alteration is located in exon 6 (coding exon 6) of the BCL7C gene. This alteration results from a G to A substitution at nucleotide position 535, causing the glutamic acid (E) at amino acid position 179 to be replaced by a lysine (K). 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

0.31

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.84

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.76

REVEL

Benign

0.14

Sift

Uncertain

0.0090

Sift4G

Benign

0.17

Polyphen

0.99

Vest4

0.58

MVP

0.56

MPC

0.25

ClinPred

0.14

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over