chr7-73553638-A-C

Variant names:

• chr7-73553638-A-C
• rs150783798
• NM_001707.4:c.93-1396T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001301061.2(BCL7B):​c.35T>G​(p.Val12Gly) variant causes a missense 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. 9/11 in silico tools predict 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_001301061.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376
• 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: Benign. The variant received -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 VariationId is 2657555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 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 GnomAdExome4. There are 17 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301061.2. 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.93-1396T>G		intron	N/A	NP_001698.2
	BCL7B	NM_001301061.2		c.35T>G	p.Val12Gly	missense	Exon 2 of 7	NP_001287990.1	F2Z3H6
	BCL7B	NM_001197244.2		c.93-1396T>G		intron	N/A	NP_001184173.1	Q9BQE9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL7B	ENST00000223368.7	TSL:1 MANE Select	c.93-1396T>G		intron	N/A	ENSP00000223368.2	Q9BQE9-1
	BCL7B	ENST00000945444.1		c.113T>G	p.Val38Gly	missense	Exon 2 of 7	ENSP00000615503.1
	BCL7B	ENST00000455335.2	TSL:3	c.35T>G	p.Val12Gly	missense	Exon 2 of 7	ENSP00000411073.2	F2Z3H6

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

African (AFR) AF: 0.00 AC: 0 AN: 52

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.0156 AC: 1 AN: 64

European-Finnish (FIN) AF: 0.00478 AC: 2 AN: 418

Middle Eastern (MID) AF: 0.0234 AC: 30 AN: 1284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.00769 AC: 1 AN: 130

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

African (AFR) AF: 0.00104 AC: 43 AN: 41416

American (AMR) AF: 0.00499 AC: 76 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00980 AC: 47 AN: 4798

European-Finnish (FIN) AF: 0.000662 AC: 7 AN: 10568

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00512 AC: 348 AN: 67942

Other (OTH) AF: 0.00855 AC: 18 AN: 2106

Alfa AF: 0.000435 Hom.: 0

Bravo AF: 0.00378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
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
PhyloP100		0.38
Sift4G	Uncertain	0.0050	D
Vest4		0.24
MVP		0.26
GERP RS		0.43
gMVP		0.14
Mutation Taster		=100/0	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: rs150783798; hg19: chr7-72967968;