1-198898549-G-T

Position:

• chr1-198898549-G-T

Variant summary

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

The NR_040073.1(MIR181A1HG):​n.363+1862C>A 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 0.724 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 NR_040073.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:2
• Conservation: PhyloP100: -0.376

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
MIR181A1HG	NR_040073.1	n.363+1862C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR181A1HG	ENST00000660348.1	n.355+1862C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109832 AN: 151692 Hom.: 40228 Cov.: 32

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.724 AC: 109921 AN: 151810 Hom.: 40262 Cov.: 32 AF XY: 0.730 AC XY: 54122 AN XY: 74158

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.702

Alfa AF: 0.695 Hom.: 4591

Bravo AF: 0.727

Asia WGS AF: 0.829 AC: 2857 AN: 3448

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

not provided Benign:1

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	-0.80
CADD	Benign	8.7
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60639710; hg19: chr1-198867678;