1-147625834-T-C

Variant names:

• chr1-147625834-T-C
• rs3766512
• NM_004326.4:c.*875T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004326.4(BCL9):​c.*875T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 232,668 control chromosomes in the GnomAD database, including 2,742 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1589 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1153 hom.)
• Consequence: BCL9 NM_004326.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 8 publications found

Genes affected

BCL9 (HGNC:1008): (BCL9 transcription coactivator) BCL9 is associated with B-cell acute lymphoblastic leukemia. It may be a target of translocation in B-cell malignancies with abnormalities of 1q21. Its function is unknown. The overexpression of BCL9 may be of pathogenic significance in B-cell malignancies. [provided by RefSeq, Jul 2008]

BCL9 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL9	NM_004326.4	c.*875T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000234739.8	NP_004317.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL9	ENST00000234739.8	c.*875T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_004326.4	ENSP00000234739.3
BCL9	ENST00000683836.1	c.*875T>C		3_prime_UTR_variant	Exon 10 of 10			ENSP00000506908.1
BCL9	ENST00000684121.1	c.*875T>C		3_prime_UTR_variant	Exon 8 of 8			ENSP00000507238.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20234 AN: 151986 Hom.: 1587 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.139 AC: 11185 AN: 80564 Hom.: 1153 Cov.: 0 AF XY: 0.138 AC XY: 5122 AN XY: 37100

African (AFR) AF: 0.163 AC: 626 AN: 3850

American (AMR) AF: 0.119 AC: 293 AN: 2466

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 364 AN: 5072

East Asian (EAS) AF: 0.366 AC: 4130 AN: 11282

South Asian (SAS) AF: 0.178 AC: 125 AN: 702

European-Finnish (FIN) AF: 0.118 AC: 59 AN: 498

Middle Eastern (MID) AF: 0.126 AC: 61 AN: 486

European-Non Finnish (NFE) AF: 0.0960 AC: 4755 AN: 49516

Other (OTH) AF: 0.115 AC: 772 AN: 6692

GnomAD4 genome AF: 0.133 AC: 20247 AN: 152104 Hom.: 1589 Cov.: 32 AF XY: 0.136 AC XY: 10132 AN XY: 74348

African (AFR) AF: 0.163 AC: 6758 AN: 41484

American (AMR) AF: 0.141 AC: 2152 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.342 AC: 1770 AN: 5172

South Asian (SAS) AF: 0.169 AC: 813 AN: 4816

European-Finnish (FIN) AF: 0.145 AC: 1536 AN: 10588

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0963 AC: 6550 AN: 67986

Other (OTH) AF: 0.129 AC: 273 AN: 2112

Alfa AF: 0.111 Hom.: 3178

Bravo AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
PhyloP100		3.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3766512; hg19: chr1-147097635;