1-198900385-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: -0.427

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -14 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 id is 427756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR181A1HG	NR_040073.1	n.363+26A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR181A1HG	ENST00000660348.1	n.355+26A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112889 AN: 151860 Hom.: 42751 Cov.: 31

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: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.743 AC: 112993 AN: 151978 Hom.: 42795 Cov.: 31 AF XY: 0.749 AC XY: 55589 AN XY: 74246

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.714

Alfa AF: 0.635 Hom.: 3351

Bravo AF: 0.750

Asia WGS AF: 0.850 AC: 2956 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

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 0.917, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.4
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10800598; hg19: chr1-198869514;