12-122054853-A-G

Position:

• chr12-122054853-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001024808.3(BCL7A):​c.488A>G​(p.Asn163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BCL7A NM_001024808.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

Genes affected

BCL7A (HGNC:1004): (BAF chromatin remodeling complex subunit BCL7A) This gene is directly involved, with Myc and IgH, in a three-way gene translocation in a Burkitt lymphoma cell line. As a result of the gene translocation, the N-terminal region of the gene product is disrupted, which is thought to be related to the pathogenesis of a subset of high-grade B cell non-Hodgkin lymphoma. The N-terminal segment involved in the translocation includes the region that shares a strong sequence similarity with those of BCL7B and BCL7C. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.085143775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL7A	NM_001024808.3	c.488A>G	p.Asn163Ser	missense_variant	5/6	ENST00000261822.5	NP_001019979.1
BCL7A	NM_020993.5	c.488A>G	p.Asn163Ser	missense_variant	5/6		NP_066273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL7A	ENST00000261822.5	c.488A>G	p.Asn163Ser	missense_variant	5/6	1	NM_001024808.3	ENSP00000261822.5
BCL7A	ENST00000538010.5	c.488A>G	p.Asn163Ser	missense_variant	5/6	1		ENSP00000445868.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2021

The c.488A>G (p.N163S) alteration is located in exon 5 (coding exon 5) of the BCL7A gene. This alteration results from a A to G substitution at nucleotide position 488, causing the asparagine (N) at amino acid position 163 to be replaced by a serine (S). 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	0.076
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.76
DEOGEN2	Benign	0.030	.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.69
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.043
Sift	Benign	0.11	T;T
Sift4G	Benign	0.82	T;T
Polyphen		0.32	B;B
Vest4		0.22
MutPred		0.20		Gain of phosphorylation at N163 (P = 0.0033);Gain of phosphorylation at N163 (P = 0.0033);
MVP		0.25
MPC		0.27
ClinPred		0.088	T
GERP RS		-0.65
Varity_R		0.028
gMVP		0.057

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: rs970494037; hg19: chr12-122492759;