rs5752638

Positions:

• chr22-27792215-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
MN1	NM_002430.3	c.3781+4548A>G		intron_variant		ENST00000302326.5	NP_002421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MN1	ENST00000302326.5	c.3781+4548A>G		intron_variant		1	NM_002430.3	ENSP00000304956	P1
MN1	ENST00000424656.1	c.134+4548A>G		intron_variant, NMD_transcript_variant		5		ENSP00000397805
MN1	ENST00000703102.1	n.306+2908A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.0937

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.192

Alfa AF: 0.219 Hom.: 7617

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

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