chr20-62564810-G-A

Variant names:

• chr20-62564810-G-A
• rs45547937
• ENST00000624914.4:n.794-179G>A

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NR_171007.1(MIR1-1HG):n.788-179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: NR_171007.1 is not a MANE Select or MANE Plus Clinical transcript for MIR1-1HG; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.232 (AC=84,166) in the gnomAD database across 363,416 control chromosomes, including 10,295 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.337. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5181 hom., cov: 35)
  • Exomes 𝑓: 0.21 (5114 hom.)
• Consequence: MIR1-1HG NR_171007.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 5 publications found

Genes affected

MIR1-1HG (HGNC:16159): (MIR1-1 host gene)

MIR133A2 (HGNC:31518): (microRNA 133a-2) 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.3367 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NR_171007.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR1-1HG	NR_171007.1		n.788-179G>A		intron	N/A
	MIR133A2	NR_029676.1		n.-102G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR1-1HG	ENST00000624914.4	TSL:1	n.794-179G>A		intron	N/A
	MIR1-1HG	ENST00000370523.4	TSL:5	n.244-5634G>A		intron	N/A
	MIR1-1HG	ENST00000686477.2		n.793-5634G>A		intron	N/A

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.255	AC:38734	Hom:5180	AN:152046	Cov:35
GnomAD4 exome	AF: 0.215	AC:45409	Hom:5114	AN:211252	Cov:
GnomAD4 genome	AF: 0.255	AC:38757	Hom:5181	AN:152164	Cov:35
TOPMed (Bravo)	AF: 0.263	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.251	AC:6379	Hom:825	AN:25374	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.266	AC:622	Hom:93	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.185	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.257	AC:77	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.139	AC:484	Hom:	AN:3476	Cov:
Korea4K (4,157 Koreans)	AF: 0.172	AC:1247	Hom:	AN:7230	Cov:
Qatari Genome	AF: 0.244	AC:43	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.111	AC:13600	Hom:761	AN:122600	Cov:
Turkish Variome	AF: 0.206	AC:318	Hom:30	AN:1546	Cov:
UK10K	AF: 0.231	AC:1748	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.183	AC:1638	Hom:154	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.124	3644	29350	0.142	9394	66238

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	4.3
BayesDel_noAF	Benign	-	-0.97
CADD	Benign	-	9.3
DANN	Benign	-	0.75
GPN-Star LLR	N/A	-	-0.67
GPN-Star score	N/A	-	0.67
Mutation Taster	N/A	polymorphism (auto)	100/0
PhyloP100	Benign	-	-0.81

Showing 8 of 8 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs45547937;

hg19: chr20-61162017;

COSMIC: COSV61525825;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar