chr3-195699434-T-C

Variant names:

• chr3-195699434-T-C
• rs9860655
• ENST00000384917.1:n.34T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NR_030296.1(MIR570):​n.34T>C 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 0.102 in 500,042 control chromosomes in the GnomAD database, including 2 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 0.078 (0 hom., cov: 44)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: MIR570 NR_030296.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 15 publications found

Genes affected

MIR570 (HGNC:32826): (microRNA 570) 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]

MUC20-OT1 (HGNC:53807): (MUC20 overlapping transcript)

MIR570HG (HGNC:53743): (MIR570 host gene)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_030296.1. 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
	MIR570	NR_030296.1		n.34T>C		non_coding_transcript_exon	Exon 1 of 1
	MIR570HG	NR_122105.1		n.401-8700T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR570	ENST00000384917.1	TSL:6	n.34T>C		non_coding_transcript_exon	Exon 1 of 1
	MUC20-OT1	ENST00000417704.6	TSL:3	n.1926-8700T>C		intron	N/A
	MUC20-OT1	ENST00000420851.6	TSL:5	n.515-8700T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11456 AN: 146672 Hom.: 0 Cov.: 44

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0695

Gnomad AMR AF: 0.0674

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.0977 AC: 21204 AN: 217076 AF XY: 0.107

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.0495

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.0136

Gnomad FIN exome AF: 0.0824

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.112 AC: 39498 AN: 353256 Hom.: 2 Cov.: 0 AF XY: 0.121 AC XY: 24167 AN XY: 200056

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0180 AC: 183 AN: 10152

American (AMR) AF: 0.0454 AC: 1545 AN: 34000

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 1093 AN: 10502

East Asian (EAS) AF: 0.0136 AC: 175 AN: 12882

South Asian (SAS) AF: 0.193 AC: 11844 AN: 61368

European-Finnish (FIN) AF: 0.0849 AC: 2556 AN: 30108

Middle Eastern (MID) AF: 0.109 AC: 292 AN: 2672

European-Non Finnish (NFE) AF: 0.115 AC: 20197 AN: 176054

Other (OTH) AF: 0.104 AC: 1613 AN: 15518

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0781 AC: 11461 AN: 146786 Hom.: 0 Cov.: 44 AF XY: 0.0768 AC XY: 5502 AN XY: 71678

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0180 AC: 742 AN: 41186

American (AMR) AF: 0.0673 AC: 988 AN: 14686

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 400 AN: 3304

East Asian (EAS) AF: 0.0123 AC: 63 AN: 5118

South Asian (SAS) AF: 0.180 AC: 814 AN: 4510

European-Finnish (FIN) AF: 0.0820 AC: 823 AN: 10042

Middle Eastern (MID) AF: 0.146 AC: 41 AN: 280

European-Non Finnish (NFE) AF: 0.113 AC: 7331 AN: 64756

Other (OTH) AF: 0.0979 AC: 197 AN: 2012

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.117 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.37
DANN	Benign	0.29
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs9860655; hg19: chr3-195426305;