Variant 16-30892900-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004765.4(BCL7C):c.220C>T(p.Arg74Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,724 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: not found (cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

BCL7C
NM_004765.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

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:

(HGNC:):

links:

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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=0.22235855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL7C	NM_004765.4 linkuse as main transcript	c.220C>T	p.Arg74Cys	missense_variant	3/6	ENST00000215115.5
MIR762HG	NR_110940.1 linkuse as main transcript	n.905-1648G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL7C	ENST00000215115.5 linkuse as main transcript	c.220C>T	p.Arg74Cys	missense_variant	3/6	1	NM_004765.4	P4	Q8WUZ0-1
MIR762HG	ENST00000570025.1 linkuse as main transcript	n.898-1648G>A		intron_variant, non_coding_transcript_variant		2
	ENST00000572471.1 linkuse as main transcript	n.293+2024C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

248354

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460724

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.220C>T (p.R74C) alteration is located in exon 3 (coding exon 3) of the BCL7C gene. This alteration results from a C to T substitution at nucleotide position 220, causing the arginine (R) at amino acid position 74 to be replaced by a cysteine (C). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.98

D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.24

N;N

REVEL

Benign

0.13

Sift

Benign

0.031

D;T

Sift4G

Uncertain

0.048

D;T

Polyphen

1.0

D;D

Vest4

0.47

MutPred

0.28

Loss of methylation at R74 (P = 0.0258);Loss of methylation at R74 (P = 0.0258);

MVP

0.48

MPC

2.6

ClinPred

0.29

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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