Genetic Variant BCL7C:p.Arg142Gln (chr16-30892603-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004765.4(BCL7C):c.425G>A(p.Arg142Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000982 in 1,425,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

BCL7C
NM_004765.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.251

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040283293).

BP6

Variant 16-30892603-C-T is Benign according to our data. Variant chr16-30892603-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2223266.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004765.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL7C	NM_004765.4	MANE Select	c.425G>A	p.Arg142Gln	missense	Exon 4 of 6	NP_004756.2
BCL7C	NM_001286526.2		c.425G>A	p.Arg142Gln	missense	Exon 4 of 6	NP_001273455.1	Q8WUZ0-2
MIR762HG	NR_110940.1		n.905-1945C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL7C	ENST00000215115.5	TSL:1 MANE Select	c.425G>A	p.Arg142Gln	missense	Exon 4 of 6	ENSP00000215115.4	Q8WUZ0-1
BCL7C	ENST00000572628.5	TSL:1	c.422G>A	p.Arg141Gln	missense	Exon 4 of 6	ENSP00000459007.1	I3L1Q2
BCL7C	ENST00000380317.8	TSL:1	c.425G>A	p.Arg142Gln	missense	Exon 4 of 6	ENSP00000369674.4	Q8WUZ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000982

AC:

AN:

1425940

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

708028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31850

American (AMR)

AF:

0.00

AC:

AN:

37164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23080

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39602

South Asian (SAS)

AF:

0.00

AC:

AN:

80230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

0.0000118

AC:

AN:

1098344

Other (OTH)

AF:

0.00

AC:

AN:

58690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.014

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.82

M_CAP

Benign

0.0094

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.22

PhyloP100

-0.25

PrimateAI

Benign

0.32

PROVEAN

Benign

0.17

REVEL

Benign

0.048

Sift

Benign

0.31

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.19

MutPred

0.20

Gain of relative solvent accessibility (P = 0.1571)

MVP

0.25

MPC

0.068

ClinPred

0.083

GERP RS

-1.7

Varity_R

0.054

gMVP

0.21

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over