Genetic Variant ENST00000606639.1:n.82+30766G>A (chr2-55983005-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4BS1BS2

The ENST00000606639.1(ENSG00000272180):n.82+30766G>A variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 532,846 control chromosomes in the GnomAD database, including 86 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 0.014 ( 25 hom., cov: 32)

Exomes 𝑓: 0.014 ( 61 hom. )

Consequence

ENSG00000272180
ENST00000606639.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.46

Publications

8 publications found

Variant links:

Genes affected

ENSG00000272180 (HGNC:):

ENSG00000272180 links:

MIR217 (HGNC:31594): (microRNA 217) 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]

MIR217 links:

MIR217HG (HGNC:50537): (MIR217 host gene)

MIR217HG links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.18).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0141 (2152/152268) while in subpopulation AMR AF = 0.0275 (421/15310). AF 95% confidence interval is 0.0253. There are 25 homozygotes in GnomAd4. There are 985 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MIR217	NR_029630.1 link	n.72C>T	non_coding_transcript_exon_variant	Exon 1 of 1
MIR217	unassigned_transcript_353	n.1C>T	non_coding_transcript_exon_variant	Exon 1 of 1
MIR217HG	NR_126406.1 link	n.209-19123C>T	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000272180	ENST00000606639.1 link	n.82+30766G>A	intron_variant	Intron 1 of 6	1
MIR217	ENST00000384817.3 link	n.72C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR217HG	ENST00000446139.2 link	n.925-19123C>T	intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2153

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00679

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0201

Gnomad OTH

AF:

0.0230

GnomAD2 exomes

AF:

0.0135

AC:

3356

AN:

247852

AF XY:

0.0135

show subpopulations

Gnomad AFR exome

AF:

0.00420

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.00511

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00947

Gnomad NFE exome

AF:

0.0202

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0140

AC:

5338

AN:

380578

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

2888

AN XY:

216602

show subpopulations

African (AFR)

AF:

0.00392

AC:

AN:

10460

American (AMR)

AF:

0.0161

AC:

577

AN:

35938

Ashkenazi Jewish (ASJ)

AF:

0.00496

AC:

AN:

11700

East Asian (EAS)

AF:

0.00

AC:

AN:

13088

South Asian (SAS)

AF:

0.00420

AC:

278

AN:

66134

European-Finnish (FIN)

AF:

0.0101

AC:

327

AN:

32222

Middle Eastern (MID)

AF:

0.00847

AC:

AN:

2834

European-Non Finnish (NFE)

AF:

0.0198

AC:

3799

AN:

191540

Other (OTH)

AF:

0.0140

AC:

234

AN:

16662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

251

502

752

1003

1254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.0141

AC:

2152

AN:

152268

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

985

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00498

AC:

207

AN:

41556

American (AMR)

AF:

0.0275

AC:

421

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00291

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00679

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0201

AC:

1366

AN:

68004

Other (OTH)

AF:

0.0227

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

108

216

325

433

541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0137

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

7.5

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