Genetic Variant MIR181A1HG:n.2225C>A (chr1-198898549-G-T) – 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.2225C>A 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 0.724 in 151,810 control chromosomes in the GnomAD database, including 40,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 40262 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

MIR181A1HG
ENST00000436880.2 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.376

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=-0.8).

BP6

Variant 1-198898549-G-T is Benign according to our data. Variant chr1-198898549-G-T is described in ClinVar as Benign. ClinVar VariationId is 427754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR181A1HG	NR_040073.1 link	n.363+1862C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR181A1HG	ENST00000436880.2 link	n.2225C>A	non_coding_transcript_exon_variant	Exon 2 of 2	1
MIR181A1HG	ENST00000653207.2 link	n.463C>A	non_coding_transcript_exon_variant	Exon 3 of 3
MIR181A1HG	ENST00000665868.3 link	n.2359C>A	non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

109832

AN:

151692

Hom.:

40228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.820

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.792

Gnomad SAS

AF:

0.876

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.701

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

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)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.724

AC:

109921

AN:

151810

Hom.:

40262

Cov.:

AF XY:

0.730

AC XY:

54122

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.820

AC:

34019

AN:

41508

American (AMR)

AF:

0.750

AC:

11427

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.777

AC:

2699

AN:

3472

East Asian (EAS)

AF:

0.792

AC:

4076

AN:

5148

South Asian (SAS)

AF:

0.876

AC:

4221

AN:

4820

European-Finnish (FIN)

AF:

0.686

AC:

7199

AN:

10498

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.650

AC:

44078

AN:

67824

Other (OTH)

AF:

0.702

AC:

1480

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1519

3038

4557

6076

7595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.681

Hom.:

50364

Bravo

AF:

0.727

Asia WGS

AF:

0.829

AC:

2857

AN:

3448

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 0.896, 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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.7

(source)

DANN

Benign

0.71

PhyloP100

-0.38

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over