Variant 22-41699535-G-GGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PVS1_StrongBP6BA1

The ENST00000401548.8(MEI1):c.-1_1dupGA(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,609,916 control chromosomes in the GnomAD database, including 2,770 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.080 ( 1346 hom., cov: 33)

Exomes 𝑓: 0.020 ( 1424 hom. )

Consequence

MEI1
ENST00000401548.8 frameshift, start_lost

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.394

Variant links:

Genes affected

MEI1 (HGNC:28613): (meiotic double-stranded break formation protein 1) Predicted to be involved in meiosis I. Predicted to act upstream of or within gamete generation; meiotic spindle organization; and meiotic telomere clustering. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MEI1 links:

MEI1 (HGNC:):

MEI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.

BP6

Variant 22-41699535-G-GGA is Benign according to our data. Variant chr22-41699535-G-GGA is described in ClinVar as [Benign]. Clinvar id is 3056418.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEI1	NM_152513.4 linkuse as main transcript	c.-1_1dupGA	p.Met1fs	frameshift_variant, start_lost	1/31	ENST00000401548.8	NP_689726.3	Q5TIA1-1Q4G0I1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEI1	ENST00000401548.8 linkuse as main transcript	c.-1_1dupGA	p.Met1fs	frameshift_variant, start_lost	1/31	1	NM_152513.4	ENSP00000384115.3		Q5TIA1-1
MEI1	ENST00000540833 linkuse as main transcript	c.-781_-780dupGA		5_prime_UTR_variant	1/20	5		ENSP00000444225.1		F5GZT0

Frequencies

GnomAD3 genomes

AF:

0.0801

AC:

12184

AN:

152166

Hom.:

1344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.0612

GnomAD3 exomes

AF:

0.0263

AC:

6300

AN:

239116

Hom.:

498

AF XY:

0.0225

AC XY:

2946

AN XY:

130768

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.0164

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.000958

Gnomad SAS exome

AF:

0.00921

Gnomad FIN exome

AF:

0.00622

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0193

GnomAD4 exome

AF:

0.0197

AC:

28658

AN:

1457632

Hom.:

1424

Cov.:

AF XY:

0.0186

AC XY:

13455

AN XY:

725002

show subpopulations

Gnomad4 AFR exome

AF:

0.262

Gnomad4 AMR exome

AF:

0.0193

Gnomad4 ASJ exome

AF:

0.0161

Gnomad4 EAS exome

AF:

0.000732

Gnomad4 SAS exome

AF:

0.0100

Gnomad4 FIN exome

AF:

0.00746

Gnomad4 NFE exome

AF:

0.0139

Gnomad4 OTH exome

AF:

0.0303

GnomAD4 genome

AF:

0.0801

AC:

12205

AN:

152284

Hom.:

1346

Cov.:

AF XY:

0.0765

AC XY:

5696

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.0325

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00973

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.0605

Alfa

AF:

0.0398

Hom.:

110

Bravo

AF:

0.0887

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MEI1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over