16-30875322-T-C

Variant names:

• chr16-30875322-T-C
• rs897984
• ENST00000572628.5:c.525+13538A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286526.2(BCL7C):​c.528+13538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 153,630 control chromosomes in the GnomAD database, including 22,386 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 0.48 (22129 hom., cov: 33)
  • Exomes 𝑓: 0.55 (257 hom.)
• Consequence: BCL7C NM_001286526.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 31 publications found

Genes affected

BCL7C (HGNC:1006): (BAF chromatin remodeling complex subunit BCL7C) This gene is identified by the similarity of its product to the N-terminal region of BCL7A protein. 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. The function of this gene has not yet been determined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

MIR762HG (HGNC:51386): (MIR762 host gene)

MIR4519 (HGNC:41544): (microRNA 4519) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286526.2. 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
	BCL7C	NM_001286526.2		c.528+13538A>G		intron	N/A	NP_001273455.1	Q8WUZ0-2
	MIR4519	NR_039744.1		n.2A>G		non_coding_transcript_exon	Exon 1 of 1
	MIR762HG	NR_110940.1		n.-138T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL7C	ENST00000572628.5	TSL:1	c.525+13538A>G		intron	N/A	ENSP00000459007.1	I3L1Q2
	BCL7C	ENST00000380317.8	TSL:1	c.528+13538A>G		intron	N/A	ENSP00000369674.4	Q8WUZ0-2
	MIR762HG	ENST00000570025.1	TSL:2	n.101T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73629 AN: 151966 Hom.: 22116 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.544

GnomAD2 exomes AF: 0.622 AC: 225 AN: 362 AF XY: 0.639

Gnomad AFR exome AF: 0.00

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.800

GnomAD4 exome AF: 0.552 AC: 854 AN: 1548 Hom.: 257 Cov.: 0 AF XY: 0.528 AC XY: 380 AN XY: 720

African (AFR) AF: 0.194 AC: 12 AN: 62

American (AMR) AF: 0.500 AC: 4 AN: 8

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.268 AC: 15 AN: 56

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.601 AC: 659 AN: 1096

European-Non Finnish (NFE) AF: 0.543 AC: 102 AN: 188

Other (OTH) AF: 0.433 AC: 58 AN: 134

GnomAD4 genome AF: 0.484 AC: 73660 AN: 152082 Hom.: 22129 Cov.: 33 AF XY: 0.488 AC XY: 36262 AN XY: 74348

African (AFR) AF: 0.128 AC: 5299 AN: 41512

American (AMR) AF: 0.649 AC: 9930 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2121 AN: 3470

East Asian (EAS) AF: 0.909 AC: 4694 AN: 5162

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4822

European-Finnish (FIN) AF: 0.658 AC: 6958 AN: 10574

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41458 AN: 67944

Other (OTH) AF: 0.542 AC: 1142 AN: 2106

Alfa AF: 0.585 Hom.: 9672

Bravo AF: 0.479

Asia WGS AF: 0.521 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.33
PhyloP100		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs897984; hg19: chr16-30886643;