chr22-27755837-G-A

Position:

• chr22-27755837-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MN1	NM_002430.3	c.3782-4741C>T		intron_variant		ENST00000302326.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MN1	ENST00000302326.5	c.3782-4741C>T		intron_variant		1	NM_002430.3	P1
MN1	ENST00000497225.1	n.138-4741C>T		intron_variant, non_coding_transcript_variant		1
MN1	ENST00000424656.1	c.135-4741C>T		intron_variant, NMD_transcript_variant		5
MN1	ENST00000703102.1	n.307-4741C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.216

Alfa AF: 0.269 Hom.: 6607

Bravo AF: 0.208

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.46
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267106; hg19: chr22-28151825;