22-27750782-A-G

Position:

• chr22-27750782-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_002430.3(MN1):​c.*133T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 345,474 control chromosomes in the GnomAD database, including 603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (517 hom., cov: 23)
  • Exomes 𝑓: 0.033 (86 hom.)
• Consequence: MN1 NM_002430.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0310

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 22-27750782-A-G is Benign according to our data. Variant chr22-27750782-A-G is described in ClinVar as [Benign]. Clinvar id is 1276500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MN1	NM_002430.3	c.*133T>C		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.*133T>C		3_prime_UTR_variant	2/2	1	NM_002430.3	ENSP00000304956	P1
MN1	ENST00000497225.1	n.452T>C		non_coding_transcript_exon_variant	2/2	1
MN1	ENST00000703102.1	n.621T>C		non_coding_transcript_exon_variant	2/2
MN1	ENST00000424656.1	c.*133T>C		3_prime_UTR_variant, NMD_transcript_variant	2/3	5		ENSP00000397805

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 6781 AN: 88458 Hom.: 513 Cov.: 23

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.000570

Gnomad EAS AF: 0.00305

Gnomad SAS AF: 0.00444

Gnomad FIN AF: 0.00158

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.00224

Gnomad OTH AF: 0.0480

GnomAD4 exome AF: 0.0333 AC: 8563 AN: 256990 Hom.: 86 Cov.: 6 AF XY: 0.0323 AC XY: 4165 AN XY: 128978

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.0607

Gnomad4 ASJ exome AF: 0.0232

Gnomad4 EAS exome AF: 0.0129

Gnomad4 SAS exome AF: 0.0363

Gnomad4 FIN exome AF: 0.0255

Gnomad4 NFE exome AF: 0.0246

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome AF: 0.0768 AC: 6792 AN: 88484 Hom.: 517 Cov.: 23 AF XY: 0.0736 AC XY: 3150 AN XY: 42780

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.0336

Gnomad4 ASJ AF: 0.000570

Gnomad4 EAS AF: 0.00306

Gnomad4 SAS AF: 0.00444

Gnomad4 FIN AF: 0.00158

Gnomad4 NFE AF: 0.00224

Gnomad4 OTH AF: 0.0476

Alfa AF: 0.123 Hom.: 845

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.6
DANN	Benign	0.87

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: rs28501997; hg19: chr22-28146770; COSMIC: COSV56561117;