7-73553638-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001707.4(BCL7B):c.93-1396T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 153,826 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 31)
  • Exomes 𝑓: 0.017 (0 hom.)
• Consequence: BCL7B NM_001707.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005997807).
• BP6: Variant 7-73553638-A-C is Benign according to our data. Variant chr7-73553638-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2657555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0173 (34/1960) while in subpopulation MID AF= 0.0234 (30/1284). AF 95% confidence interval is 0.0168. There are 0 homozygotes in gnomad4_exome. There are 17 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL7B	NM_001707.4	c.93-1396T>G		intron_variant		ENST00000223368.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL7B	ENST00000223368.7	c.93-1396T>G		intron_variant		1	NM_001707.4	P1

Frequencies

GnomAD3 genomes AF: 0.00387 AC: 587 AN: 151746 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00500

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00979

Gnomad FIN AF: 0.000662

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00512

Gnomad OTH AF: 0.00864

GnomAD4 exome AF: 0.0173 AC: 34 AN: 1960 Hom.: 0 Cov.: 0 AF XY: 0.0166 AC XY: 17 AN XY: 1024

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.0156

Gnomad4 FIN exome AF: 0.00478

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00769

GnomAD4 genome AF: 0.00385 AC: 584 AN: 151866 Hom.: 2 Cov.: 31 AF XY: 0.00372 AC XY: 276 AN XY: 74200

Gnomad4 AFR AF: 0.00104

Gnomad4 AMR AF: 0.00499

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00980

Gnomad4 FIN AF: 0.000662

Gnomad4 NFE AF: 0.00512

Gnomad4 OTH AF: 0.00855

Alfa AF: 0.000435 Hom.: 0

Bravo AF: 0.00378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

BCL7B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.1
DANN	Benign	0.63
DEOGEN2	Benign	0.39	T
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0060	T
MutationTaster	Benign	1.0	N;N
Sift4G	Uncertain	0.0050	D
Vest4		0.24
MVP		0.26
GERP RS		0.43
gMVP		0.14

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: rs150783798; hg19: chr7-72967968;