16-30892603-C-T

Position:

• chr16-30892603-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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. 15/21 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.251

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)

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 2223266.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL7C	NM_004765.4	c.425G>A	p.Arg142Gln	missense_variant	4/6	ENST00000215115.5
MIR762HG	NR_110940.1	n.905-1945C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL7C	ENST00000215115.5	c.425G>A	p.Arg142Gln	missense_variant	4/6	1	NM_004765.4	P4
MIR762HG	ENST00000570025.1	n.898-1945C>T		intron_variant, non_coding_transcript_variant		2
	ENST00000572471.1	n.293+2321G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000982 AC: 14 AN: 1425940 Hom.: 0 Cov.: 32 AF XY: 0.0000127 AC XY: 9 AN XY: 708028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000118

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.74
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.22	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.048
Sift	Benign	0.31	T;T
Sift4G	Benign	0.87	T;T
Polyphen		0.0	B;B
Vest4		0.19
MutPred		0.20		Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);
MVP		0.25
MPC		0.068
ClinPred		0.083	T
GERP RS		-1.7
Varity_R		0.054
gMVP		0.21

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

Other links and lift over

dbSNP: rs2055265308; hg19: chr16-30903924; COSMIC: COSV53064055; COSMIC: COSV53064055;