rs5752638

Variant names:

• chr22-27792215-T-C
• rs5752638
• NM_002430.3:c.3781+4548A>G

Variant summary

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

The NM_002430.3(MN1):​c.3781+4548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,160 control chromosomes in the GnomAD database, including 2,684 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 0.17 (2684 hom., cov: 30)
• Consequence: MN1 NM_002430.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 4 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MN1	NM_002430.3	c.3781+4548A>G		intron_variant	Intron 1 of 1	ENST00000302326.5	NP_002421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MN1	ENST00000302326.5	c.3781+4548A>G		intron_variant	Intron 1 of 1	1	NM_002430.3	ENSP00000304956.4
MN1	ENST00000424656.1	n.133+4548A>G		intron_variant	Intron 1 of 2	5		ENSP00000397805.1
MN1	ENST00000703102.1	n.306+2908A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26049 AN: 151062 Hom.: 2683 Cov.: 30

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.172 AC: 26051 AN: 151160 Hom.: 2684 Cov.: 30 AF XY: 0.173 AC XY: 12777 AN XY: 73828

African (AFR) AF: 0.0682 AC: 2819 AN: 41320

American (AMR) AF: 0.191 AC: 2908 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3462

East Asian (EAS) AF: 0.0937 AC: 482 AN: 5146

South Asian (SAS) AF: 0.287 AC: 1369 AN: 4772

European-Finnish (FIN) AF: 0.178 AC: 1811 AN: 10192

Middle Eastern (MID) AF: 0.253 AC: 73 AN: 288

European-Non Finnish (NFE) AF: 0.219 AC: 14821 AN: 67804

Other (OTH) AF: 0.192 AC: 401 AN: 2084

Alfa AF: 0.208 Hom.: 10978

Bravo AF: 0.168

Asia WGS AF: 0.162 AC: 562 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.3
DANN	Benign	0.68
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5752638; hg19: chr22-28188203; COSMIC: COSV56563520; COSMIC: COSV56563520;