rs2267106

Variant names:

• chr22-27755837-G-A
• rs2267106
• NM_002430.3:c.3782-4741C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002430.3(MN1):​c.3782-4741C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,172 control chromosomes in the GnomAD database, including 3,998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3998 hom., cov: 32)
• Consequence: MN1 NM_002430.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 1 publications found

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]

MN1 Gene-Disease associations (from GenCC):

• CEBALID syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• familial meningioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002430.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	NM_002430.3	MANE Select	c.3782-4741C>T		intron	N/A	NP_002421.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	ENST00000302326.5	TSL:1 MANE Select	c.3782-4741C>T		intron	N/A	ENSP00000304956.4	Q10571
	MN1	ENST00000497225.1	TSL:1	n.138-4741C>T		intron	N/A
	MN1	ENST00000424656.1	TSL:5	n.134-4741C>T		intron	N/A	ENSP00000397805.1	H7C105

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32925 AN: 152054 Hom.: 3998 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.218

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32930 AN: 152172 Hom.: 3998 Cov.: 32 AF XY: 0.213 AC XY: 15861 AN XY: 74386

African (AFR) AF: 0.118 AC: 4893 AN: 41534

American (AMR) AF: 0.186 AC: 2840 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3468

East Asian (EAS) AF: 0.187 AC: 963 AN: 5162

South Asian (SAS) AF: 0.143 AC: 688 AN: 4826

European-Finnish (FIN) AF: 0.252 AC: 2664 AN: 10572

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19239 AN: 68004

Other (OTH) AF: 0.216 AC: 456 AN: 2114

Alfa AF: 0.261 Hom.: 8727

Bravo AF: 0.208

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.46
DANN	Benign	0.49
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2267106; hg19: chr22-28151825;