rs9660525

chr1-198807802-C-Achr1-198807802-C-T

Variant summary

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

The ENST00000660348.1(MIR181A1HG):n.356-28499G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,026 control chromosomes in the GnomAD database, including 12,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12186 hom., cov: 32)
  • Exomes 𝑓: 0.45 (3 hom.)
• Consequence: MIR181A1HG ENST00000660348.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: 0.658

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=-0.95).
• BP6: Variant 1-198807802-C-A is Benign according to our data. Variant chr1-198807802-C-A is described in ClinVar as [Benign]. Clinvar id is 427752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR181A1HG	ENST00000660348.1	n.356-28499G>T		intron_variant, non_coding_transcript_variant
MIR181A1HG	ENST00000412162.1	n.633G>T		non_coding_transcript_exon_variant	2/2	3
MIR181A1HG	ENST00000432296.1	n.786G>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59645 AN: 151886 Hom.: 12165 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.401

GnomAD4 exome AF: 0.455 AC: 10 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.393 AC: 59707 AN: 152004 Hom.: 12186 Cov.: 32 AF XY: 0.402 AC XY: 29885 AN XY: 74310

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.402

Alfa AF: 0.383 Hom.: 3188

Bravo AF: 0.389

Asia WGS AF: 0.540 AC: 1876 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 0.188, 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	-0.95
Cadd	Benign	3.6
Dann	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9660525; hg19: chr1-198776931;