Genetic Variant MIR181A1HG:n.389A>G (chr1-198900385-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000436880.2(MIR181A1HG):n.389A>G 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 0.743 in 151,980 control chromosomes in the GnomAD database, including 42,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42795 hom., cov: 31)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

MIR181A1HG
ENST00000436880.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: -0.427

Publications

2 publications found

Variant links:

Genes affected

MIR181A1HG (HGNC:48659): (MIR181A1 host gene)

MIR181A1HG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-198900385-T-C is Benign according to our data. Variant chr1-198900385-T-C is described in ClinVar as Benign. ClinVar VariationId is 427756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000436880.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR181A1HG	NR_040073.1		n.363+26A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
MIR181A1HG	ENST00000436880.2	TSL:1	n.389A>G	non_coding_transcript_exon	Exon 2 of 2
MIR181A1HG	ENST00000665868.3		n.523A>G	non_coding_transcript_exon	Exon 2 of 2
MIR181A1HG	ENST00000806898.1		n.590A>G	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

112889

AN:

151860

Hom.:

42751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.879

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.757

Gnomad ASJ

AF:

0.780

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.877

Gnomad FIN

AF:

0.684

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.713

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.743

AC:

112993

AN:

151978

Hom.:

42795

Cov.:

AF XY:

0.749

AC XY:

55589

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.879

AC:

36496

AN:

41532

American (AMR)

AF:

0.758

AC:

11549

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.780

AC:

2707

AN:

3470

East Asian (EAS)

AF:

0.829

AC:

4256

AN:

5132

South Asian (SAS)

AF:

0.877

AC:

4225

AN:

4818

European-Finnish (FIN)

AF:

0.684

AC:

7218

AN:

10556

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.652

AC:

44305

AN:

67912

Other (OTH)

AF:

0.714

AC:

1510

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1426

2852

4278

5704

7130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

850

1700

2550

3400

4250

<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:

0.691

Hom.:

10295

Bravo

AF:

0.750

Asia WGS

AF:

0.850

AC:

2956

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Acute myeloblastic leukemia with maturation

Pathogenic:1

Fujian Institute of Hematology, Fujian Medical University

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:case-control

This variant contributes to development of AML-M2

not specified

Benign:1

Oct 28, 2020

H3Africa Consortium

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.917, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

(source)

DANN

Benign

0.77

PhyloP100

-0.43

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over