rs10800597

Positions:

• chr1-198898955-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000436880.2(MIR181A1HG):​n.1819C>T 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 151,930 control chromosomes in the GnomAD database, including 40,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40351 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MIR181A1HG ENST00000436880.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:2
• Conservation: PhyloP100: -0.819

Genes affected

MIR181A1HG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-198898955-G-A is Benign according to our data. Variant chr1-198898955-G-A is described in ClinVar as [Benign]. Clinvar id is 427755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR181A1HG	NR_040073.1	n.363+1456C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR181A1HG	ENST00000436880.2	n.1819C>T		non_coding_transcript_exon_variant	2/2	1
MIR181A1HG	ENST00000665868.2	n.1861C>T		non_coding_transcript_exon_variant	2/2
MIR181A1HG	ENST00000432296.1	n.344+1456C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109963 AN: 151812 Hom.: 40313 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.702

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.724 AC: 110059 AN: 151930 Hom.: 40351 Cov.: 32 AF XY: 0.730 AC XY: 54176 AN XY: 74210

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.704

Alfa AF: 0.695 Hom.: 4592

Bravo AF: 0.728

Asia WGS AF: 0.831 AC: 2884 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Acute myeloblastic leukemia with maturation Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Fujian Institute of Hematology, Fujian Medical University

-

This variant contributes to development of AML-M2 -

not specified Benign:1

Benign, criteria provided, single submitter

research

H3Africa Consortium

Oct 28, 2020

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.875, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10800597; hg19: chr1-198868084;