rs72631823

Variant names:

• chr1-9151723-C-T
• rs72631823
• ENST00000635687.1:n.499G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000635687.1(MIR34AHG):​n.499G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 536,686 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: MIR34AHG ENST00000635687.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 14 publications found

Genes affected

MIR34AHG (HGNC:51913): (MIR34A host gene)

MIR34A (HGNC:31635): (microRNA 34a) 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. This miRNA is a member of the highly conserved miR-34 family. This miRNA functions as a tumor suppressor and dysregulation or loss of the host gene from which this miRNA is processed is associated with cancer progression in numerous cell types. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635687.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR34A	NR_029610.1		n.55G>A		non_coding_transcript_exon	Exon 1 of 1
	MIR34AHG	NR_132742.1		n.445G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR34AHG	ENST00000635687.1	TSL:1	n.499G>A		non_coding_transcript_exon	Exon 2 of 2
	MIR34A	ENST00000385130.1	TSL:6	n.55G>A		non_coding_transcript_exon	Exon 1 of 1
	MIR34AHG	ENST00000782879.1		n.464-11702G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251078 AF XY: 0.0000736

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000572 AC: 22 AN: 384362 Hom.: 0 Cov.: 0 AF XY: 0.0000503 AC XY: 11 AN XY: 218722

African (AFR) AF: 0.00189 AC: 20 AN: 10566

American (AMR) AF: 0.0000275 AC: 1 AN: 36322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11778

East Asian (EAS) AF: 0.00 AC: 0 AN: 13408

South Asian (SAS) AF: 0.0000150 AC: 1 AN: 66776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2858

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 193322

Other (OTH) AF: 0.00 AC: 0 AN: 16810

GnomAD4 genome AF: 0.000387 AC: 59 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74488

African (AFR) AF: 0.00140 AC: 58 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000173 Hom.: 0

Bravo AF: 0.000419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs72631823; hg19: chr1-9211782;