chr22-27750781-GA-G

Position:

• chr22-27750781-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002430.3(MN1):​c.*133del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 493,890 control chromosomes in the GnomAD database, including 181 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (68 hom., cov: 23)
  • Exomes 𝑓: 0.040 (113 hom.)
• Consequence: MN1 NM_002430.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0310

Genes affected

MN1 (HGNC:7180): (MN1 proto-oncogene, transcriptional regulator) Meningioma 1 (MN1) contains two sets of CAG repeats. It is disrupted by a balanced translocation (4;22) in a meningioma, and its inactivation may contribute to meningioma 32 pathogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-27750781-GA-G is Benign according to our data. Variant chr22-27750781-GA-G is described in ClinVar as [Benign]. Clinvar id is 1271009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MN1	NM_002430.3	c.*133del		3_prime_UTR_variant	2/2	ENST00000302326.5	NP_002421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MN1	ENST00000302326.5	c.*133del		3_prime_UTR_variant	2/2	1	NM_002430.3	ENSP00000304956	P1
MN1	ENST00000497225.1	n.452del		non_coding_transcript_exon_variant	2/2	1
MN1	ENST00000703102.1	n.621del		non_coding_transcript_exon_variant	2/2
MN1	ENST00000424656.1	c.*133del		3_prime_UTR_variant, NMD_transcript_variant	2/3	5		ENSP00000397805

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 3836 AN: 41374 Hom.: 68 Cov.: 23

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0459

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.0263

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0403 AC: 18247 AN: 452488 Hom.: 113 Cov.: 6 AF XY: 0.0394 AC XY: 8993 AN XY: 228008

Gnomad4 AFR exome AF: 0.0134

Gnomad4 AMR exome AF: 0.0201

Gnomad4 ASJ exome AF: 0.0413

Gnomad4 EAS exome AF: 0.0176

Gnomad4 SAS exome AF: 0.0200

Gnomad4 FIN exome AF: 0.0235

Gnomad4 NFE exome AF: 0.0468

Gnomad4 OTH exome AF: 0.0362

GnomAD4 genome AF: 0.0927 AC: 3837 AN: 41402 Hom.: 68 Cov.: 23 AF XY: 0.0878 AC XY: 1720 AN XY: 19580

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0459

Gnomad4 SAS AF: 0.0392

Gnomad4 FIN AF: 0.0478

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.103

Alfa AF: 0.00698 Hom.: 2

Bravo AF: 0.0266

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs377485634; hg19: chr22-28146769;