16-30892603-C-G

Variant names:

• chr16-30892603-C-G
• rs2055265308
• NM_004765.4:c.425G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004765.4(BCL7C):​c.425G>C​(p.Arg142Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R142Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BCL7C NM_004765.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 0 publications found

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]

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

ENSG00000262721 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08198485).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL7C	NM_004765.4	MANE Select	c.425G>C	p.Arg142Pro	missense	Exon 4 of 6	NP_004756.2
	BCL7C	NM_001286526.2		c.425G>C	p.Arg142Pro	missense	Exon 4 of 6	NP_001273455.1	Q8WUZ0-2
	MIR762HG	NR_110940.1		n.905-1945C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL7C	ENST00000215115.5	TSL:1 MANE Select	c.425G>C	p.Arg142Pro	missense	Exon 4 of 6	ENSP00000215115.4	Q8WUZ0-1
	BCL7C	ENST00000572628.5	TSL:1	c.422G>C	p.Arg141Pro	missense	Exon 4 of 6	ENSP00000459007.1	I3L1Q2
	BCL7C	ENST00000380317.8	TSL:1	c.425G>C	p.Arg142Pro	missense	Exon 4 of 6	ENSP00000369674.4	Q8WUZ0-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.25
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.033
Sift	Benign	0.078	T
Sift4G	Benign	0.28	T
Polyphen		0.17	B
Vest4		0.27
MutPred		0.22		Gain of glycosylation at R142 (P = 0.0373)
MVP		0.42
MPC		0.085
ClinPred		0.099	T
GERP RS		-1.7
Varity_R		0.21
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2055265308; hg19: chr16-30903924;