rs1311987894

Variant names:

• chr12-122054967-G-A
• rs1311987894
• ENST00000538010.5:c.602G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020993.5(BCL7A):​c.602G>A​(p.Arg201Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000062 (0 hom.)
• Consequence: BCL7A NM_020993.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.83
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031784356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020993.5. 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
	BCL7A	NM_001024808.3	MANE Select	c.561+41G>A		intron	N/A	NP_001019979.1	Q4VC05-1
	BCL7A	NM_020993.5		c.602G>A	p.Arg201Gln	missense	Exon 5 of 6	NP_066273.1	Q4VC05-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL7A	ENST00000538010.5	TSL:1	c.602G>A	p.Arg201Gln	missense	Exon 5 of 6	ENSP00000445868.1	Q4VC05-2
	BCL7A	ENST00000261822.5	TSL:1 MANE Select	c.561+41G>A		intron	N/A	ENSP00000261822.5	Q4VC05-1
	BCL7A	ENST00000918381.1		c.645+41G>A		intron	N/A	ENSP00000588440.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251050 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461744 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727178

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111974

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.24
DANN	Benign	0.89
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.8
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.0070
Sift	Benign	0.52	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.076
MutPred		0.23		Gain of catalytic residue at L206 (P = 0.0029)
MVP		0.14
MPC		0.35
ClinPred		0.041	T
GERP RS		-9.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.087
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1311987894; hg19: chr12-122492873; COSMIC: COSV99947180;