Genetic Variant MIR181A1HG:n.191+35G>A (chr1-198826991-C-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 ENST00000412162.1(MIR181A1HG):n.191+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,036 control chromosomes in the GnomAD database, including 18,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18890 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

MIR181A1HG
ENST00000412162.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.401

Publications

3 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=-0.89).

BP6

Variant 1-198826991-C-T is Benign according to our data. Variant chr1-198826991-C-T is described in ClinVar as Benign. ClinVar VariationId is 427753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR181A1HG	NR_040073.1 link	n.364-18748G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR181A1HG	ENST00000412162.1 link	n.191+35G>A	intron_variant	Intron 1 of 1	3
MIR181A1HG	ENST00000432296.2 link	n.364-18748G>A	intron_variant	Intron 2 of 2	3
MIR181A1HG	ENST00000660348.1 link	n.356-47688G>A	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73554

AN:

151918

Hom.:

18876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.592

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.489

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:

0.484

AC:

73608

AN:

152036

Hom.:

18890

Cov.:

AF XY:

0.493

AC XY:

36646

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.302

AC:

12517

AN:

41444

American (AMR)

AF:

0.576

AC:

8801

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

1989

AN:

3470

East Asian (EAS)

AF:

0.572

AC:

2951

AN:

5156

South Asian (SAS)

AF:

0.688

AC:

3317

AN:

4818

European-Finnish (FIN)

AF:

0.592

AC:

6261

AN:

10578

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36213

AN:

67962

Other (OTH)

AF:

0.489

AC:

1034

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1873

3746

5619

7492

9365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.513

Hom.:

2603

Bravo

AF:

0.469

Asia WGS

AF:

0.576

AC:

2003

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 0.167, 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

-0.89

CADD

Benign

0.97

(source)

DANN

Benign

0.63

PhyloP100

-0.40

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