7-73557563-C-T

Variant names:

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

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>A​(p.Val6Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,210,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V6L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: BCL7B NM_001707.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.99
• Publications: 0 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=0.27379888).

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>A	p.Val6Ile	missense	Exon 1 of 6	NP_001698.2
	BCL7B	NM_001197244.2		c.16G>A	p.Val6Ile	missense	Exon 1 of 5	NP_001184173.1	Q9BQE9-4
	BCL7B	NM_001301061.2		c.-74G>A		5_prime_UTR	Exon 1 of 7	NP_001287990.1	F2Z3H6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL7B	ENST00000223368.7	TSL:1 MANE Select	c.16G>A	p.Val6Ile	missense	Exon 1 of 6	ENSP00000223368.2	Q9BQE9-1
	BCL7B	ENST00000945444.1		c.16G>A	p.Val6Ile	missense	Exon 1 of 7	ENSP00000615503.1
	BCL7B	ENST00000871802.1		c.16G>A	p.Val6Ile	missense	Exon 1 of 7	ENSP00000541861.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000165 AC: 2 AN: 1210056 Hom.: 0 Cov.: 31 AF XY: 0.00000169 AC XY: 1 AN XY: 593200

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

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: 0.00000205 AC: 2 AN: 976328

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		7.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.16
Sift	Benign	0.15	T
Sift4G	Benign	0.24	T
Polyphen		0.015	B
Vest4		0.14
MutPred		0.51		Gain of catalytic residue at V6 (P = 0.0416)
MVP		0.34
MPC		1.2
ClinPred		0.94	D
GERP RS		2.5
PromoterAI		0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.11
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;