Genetic Variant ENST00000784740.1:n.121-4365C>T (chr6-52144499-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000784740.1(ENSG00000302165):n.121-4365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 480,818 control chromosomes in the GnomAD database, including 11 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 0.0057 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 9 hom. )

Consequence

ENSG00000302165
ENST00000784740.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

13 publications found

Variant links:

Genes affected

ENSG00000302165 (HGNC:):

ENSG00000302165 links:

MIR206 (HGNC:31584): (microRNA 206) 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. Disruption of the encoded miRNA has been implicated in multiple skeletal muscle disorders, including amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD), as well as in several cancers. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Aug 2017]

MIR206 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00618 (2029/328476) while in subpopulation MID AF = 0.022 (56/2542). AF 95% confidence interval is 0.0174. There are 9 homozygotes in GnomAdExome4. There are 1073 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR206	NR_029713.1 link	n.*65C>T		downstream_gene_variant
MIR206	unassigned_transcript_1138	n.*77C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302165	ENST00000784740.1 link	n.121-4365C>T		intron_variant	Intron 1 of 1
MIR206	ENST00000384872.3 link	n.*65C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.00568

AC:

865

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00858

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.00618

AC:

2029

AN:

328476

Hom.:

AF XY:

0.00586

AC XY:

1073

AN XY:

183158

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

9664

American (AMR)

AF:

0.00528

AC:

169

AN:

32004

Ashkenazi Jewish (ASJ)

AF:

0.00372

AC:

AN:

10210

East Asian (EAS)

AF:

0.00

AC:

AN:

12006

South Asian (SAS)

AF:

0.00254

AC:

153

AN:

60324

European-Finnish (FIN)

AF:

0.00124

AC:

AN:

30742

Middle Eastern (MID)

AF:

0.0220

AC:

AN:

2542

European-Non Finnish (NFE)

AF:

0.00922

AC:

1443

AN:

156562

Other (OTH)

AF:

0.00784

AC:

113

AN:

14422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

182

274

365

456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00568

AC:

865

AN:

152342

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

407

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

41580

American (AMR)

AF:

0.00869

AC:

133

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00858

AC:

584

AN:

68030

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00706

Hom.:

Bravo

AF:

0.00629

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.8

(source)

DANN

Benign

0.83

PhyloP100

-1.2

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