7-73557563-C-G

Variant names:

• chr7-73557563-C-G
• rs1295157268
• NM_001707.4:c.16G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001707.4(BCL7B):​c.16G>C​(p.Val6Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000441 in 1,361,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: BCL7B NM_001707.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.99
• Publications: 1 publications found

Genes affected

BCL7B (HGNC:1005): (BAF chromatin remodeling complex subunit BCL7B) This gene encodes a member of the BCL7 family including BCL7A, BCL7B and BCL7C proteins. This member is BCL7B, which contains a region that is highly similar to the N-terminal segment of BCL7A or BCL7C proteins. 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. This gene is located at a chromosomal region commonly deleted in Williams syndrome. This gene is highly conserved from C. elegans to human. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29234666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001707.4. 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
	BCL7B	NM_001707.4	MANE Select	c.16G>C	p.Val6Leu	missense	Exon 1 of 6	NP_001698.2
	BCL7B	NM_001197244.2		c.16G>C	p.Val6Leu	missense	Exon 1 of 5	NP_001184173.1
	BCL7B	NM_001301061.2		c.-74G>C		5_prime_UTR	Exon 1 of 7	NP_001287990.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL7B	ENST00000223368.7	TSL:1 MANE Select	c.16G>C	p.Val6Leu	missense	Exon 1 of 6	ENSP00000223368.2
	BCL7B	ENST00000945444.1		c.16G>C	p.Val6Leu	missense	Exon 1 of 7	ENSP00000615503.1
	BCL7B	ENST00000871802.1		c.16G>C	p.Val6Leu	missense	Exon 1 of 7	ENSP00000541861.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151400 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 100346 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000413 AC: 5 AN: 1210056 Hom.: 0 Cov.: 31 AF XY: 0.00000337 AC XY: 2 AN XY: 593200

African (AFR) AF: 0.00 AC: 0 AN: 24752

American (AMR) AF: 0.00 AC: 0 AN: 20122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18758

East Asian (EAS) AF: 0.00 AC: 0 AN: 27472

South Asian (SAS) AF: 0.00 AC: 0 AN: 50418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3292

European-Non Finnish (NFE) AF: 0.00000512 AC: 5 AN: 976328

Other (OTH) AF: 0.00 AC: 0 AN: 47170

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151400 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73964

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67794

Other (OTH) AF: 0.00 AC: 0 AN: 2076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		7.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.16
Sift	Benign	0.084	T
Sift4G	Benign	0.11	T
Polyphen		0.015	B
Vest4		0.21
MutPred		0.52		Loss of sheet (P = 0.0817)
MVP		0.32
MPC		1.4
ClinPred		0.91	D
GERP RS		2.5
PromoterAI		0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.27
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs1295157268; hg19: chr7-72971893;