22-27750780-A-AG

Position:

• chr22-27750780-A-AG

Variant summary

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

The NM_002430.3(MN1):​c.*134_*135insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (15393 hom., cov: 0)
  • Exomes 𝑓: 0.34 (15954 hom.)
• Consequence: MN1 NM_002430.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.178

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 22-27750780-A-AG is Benign according to our data. Variant chr22-27750780-A-AG is described in ClinVar as [Benign]. Clinvar id is 1265884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MN1	NM_002430.3	c.*134_*135insC		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.*134_*135insC		3_prime_UTR_variant	2/2	1	NM_002430.3	ENSP00000304956	P1
MN1	ENST00000497225.1	n.453_454insC		non_coding_transcript_exon_variant	2/2	1
MN1	ENST00000703102.1	n.622_623insC		non_coding_transcript_exon_variant	2/2
MN1	ENST00000424656.1	c.*134_*135insC		3_prime_UTR_variant, NMD_transcript_variant	2/3	5		ENSP00000397805

Frequencies

GnomAD3 genomes AF: 0.457 AC: 66707 AN: 146112 Hom.: 15381 Cov.: 0

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.343 AC: 177289 AN: 516678 Hom.: 15954 Cov.: 8 AF XY: 0.342 AC XY: 89565 AN XY: 261650

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.457 AC: 66746 AN: 146182 Hom.: 15393 Cov.: 0 AF XY: 0.454 AC XY: 32244 AN XY: 70994

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.469

Asia WGS AF: 0.356 AC: 1225 AN: 3444

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 13, 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: rs11379447; hg19: chr22-28146768;