Genetic Variant ENST00000624914.4:n.793+643G>A (chr20-62554308-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The ENST00000624914.4(MIR1-1HG):n.793+643G>A variant causes a intron change. The variant allele was found at a frequency of 0.00218 in 522,358 control chromosomes in the GnomAD database, including 9 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 0.0058 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

MIR1-1HG
ENST00000624914.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.02

Publications

8 publications found

Variant links:

Genes affected

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

MIR1-1HG links:

MIR1-1 (HGNC:31499): (microRNA 1-1) 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]

MIR1-1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

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

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0058 (883/152324) while in subpopulation AFR AF = 0.0202 (840/41568). AF 95% confidence interval is 0.0191. There are 9 homozygotes in GnomAd4. There are 404 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MIR1-1	NR_029780.1 link	n.3G>A	non_coding_transcript_exon_variant	Exon 1 of 1
MIR1-1HG	NR_171007.1 link	n.787+643G>A	intron_variant	Intron 2 of 3
MIR1-1	unassigned_transcript_3475	n.-4G>A	upstream_gene_variant
MIR1-1	unassigned_transcript_3476	n.-43G>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR1-1HG	ENST00000624914.4 link	n.793+643G>A	intron_variant	Intron 2 of 3	1
MIR1-1	ENST00000362147.2 link	n.3G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR1-1HG	ENST00000370523.4 link	n.243+643G>A	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00576

AC:

877

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

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:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00148

AC:

371

AN:

250398

AF XY:

0.00105

show subpopulations

Gnomad AFR exome

AF:

0.0201

Gnomad AMR exome

AF:

0.000927

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

AF:

0.000689

AC:

255

AN:

370034

Hom.:

Cov.:

AF XY:

0.000463

AC XY:

AN XY:

209638

show subpopulations

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

African (AFR)

AF:

0.0197

AC:

202

AN:

10270

American (AMR)

AF:

0.000885

AC:

AN:

36152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11558

East Asian (EAS)

AF:

0.00

AC:

AN:

12798

South Asian (SAS)

AF:

0.0000453

AC:

AN:

66158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31692

Middle Eastern (MID)

AF:

0.000797

AC:

AN:

2508

European-Non Finnish (NFE)

AF:

0.0000164

AC:

AN:

182776

Other (OTH)

AF:

0.000806

AC:

AN:

16122

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.399

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00580

AC:

883

AN:

152324

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

404

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0202

AC:

840

AN:

41568

American (AMR)

AF:

0.00242

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68016

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00693

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

4.0

Mutation Taster

=97/3

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over