11-111513121-C-T

Variant names:

• chr11-111513121-C-T
• rs2187473
• NM_001367974.1:c.-27+1546G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367974.1(BTG4):​c.-27+1546G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 405,722 control chromosomes in the GnomAD database, including 6,717 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 (1599 hom., cov: 33)
  • Exomes 𝑓: 0.19 (5118 hom.)
• Consequence: BTG4 NM_001367974.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

Genes affected

BTG4 (HGNC:13862): (BTG anti-proliferation factor 4) The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein can induce G1 arrest in the cell cycle. [provided by RefSeq, Jul 2008]

MIR34BHG (HGNC:55987): (MIR34B and MIR34C host gene)

MIR34B (HGNC:31636): (microRNA 34b) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTG4	NM_001367974.1	c.-27+1546G>A		intron_variant	Intron 1 of 4		NP_001354903.1
BTG4	XM_024448589.2	c.-27+1546G>A		intron_variant	Intron 1 of 7		XP_024304357.1
BTG4	XM_024448591.2	c.-27+1097G>A		intron_variant	Intron 1 of 7		XP_024304359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTG4	ENST00000689553.1	c.-207-844G>A		intron_variant	Intron 1 of 6			ENSP00000508793.1
MIR34BHG	ENST00000651138.1	n.377C>T		non_coding_transcript_exon_variant	Exon 2 of 2
MIR34B	ENST00000385076.3	n.*100C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19548 AN: 152116 Hom.: 1594 Cov.: 33

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.192 AC: 48671 AN: 253488 Hom.: 5118 AF XY: 0.204 AC XY: 28328 AN XY: 138804

Gnomad4 AFR exome AF: 0.0361

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.129 AC: 19564 AN: 152234 Hom.: 1599 Cov.: 33 AF XY: 0.131 AC XY: 9718 AN XY: 74430

Gnomad4 AFR AF: 0.0329

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0680 Hom.: 93

Bravo AF: 0.122

Asia WGS AF: 0.251 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2187473; hg19: chr11-111383846; COSMIC: COSV60442174;