NM_001367974.1:c.-27+1546G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367974.1. 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
	BTG4	NM_001367974.1		c.-27+1546G>A		intron	N/A	NP_001354903.1
	MIR34BHG	NR_147706.1		n.375C>T		non_coding_transcript_exon	Exon 2 of 2
	MIR34B	NR_029839.1		n.*100C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTG4	ENST00000689553.1		c.-207-844G>A		intron	N/A	ENSP00000508793.1
	MIR34BHG	ENST00000651138.2		n.382C>T		non_coding_transcript_exon	Exon 2 of 2
	MIR34BHG	ENST00000726427.1		n.489C>T		non_coding_transcript_exon	Exon 3 of 3

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

African (AFR) AF: 0.0361 AC: 225 AN: 6236

American (AMR) AF: 0.213 AC: 4389 AN: 20612

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 1277 AN: 8168

East Asian (EAS) AF: 0.166 AC: 1237 AN: 7444

South Asian (SAS) AF: 0.297 AC: 15138 AN: 50980

European-Finnish (FIN) AF: 0.171 AC: 4355 AN: 25442

Middle Eastern (MID) AF: 0.193 AC: 200 AN: 1036

European-Non Finnish (NFE) AF: 0.162 AC: 19855 AN: 122198

Other (OTH) AF: 0.175 AC: 1995 AN: 11372

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

African (AFR) AF: 0.0329 AC: 1369 AN: 41554

American (AMR) AF: 0.161 AC: 2457 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.160 AC: 829 AN: 5172

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4824

European-Finnish (FIN) AF: 0.164 AC: 1734 AN: 10596

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10771 AN: 67998

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.0743 Hom.: 114

Bravo AF: 0.122

Asia WGS AF: 0.251 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.79
PhyloP100		-0.094
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

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