chr22-27750781-GA-G

Variant names:

• chr22-27750781-GA-G
• rs377485634
• NM_002430.3:c.*133delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002430.3(MN1):​c.*133delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 493,890 control chromosomes in the GnomAD database, including 181 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (68 hom., cov: 23)
  • Exomes 𝑓: 0.040 (113 hom.)
• Consequence: MN1 NM_002430.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0310
• Publications: 0 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial meningioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 22-27750781-GA-G is Benign according to our data. Variant chr22-27750781-GA-G is described in ClinVar as Benign. ClinVar VariationId is 1271009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.118 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.*133delT		3_prime_UTR	Exon 2 of 2	NP_002421.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MN1	ENST00000302326.5	TSL:1 MANE Select	c.*133delT		3_prime_UTR	Exon 2 of 2	ENSP00000304956.4	Q10571
	MN1	ENST00000497225.1	TSL:1	n.452delT		non_coding_transcript_exon	Exon 2 of 2
	MN1	ENST00000424656.1	TSL:5	n.*133delT		non_coding_transcript_exon	Exon 2 of 3	ENSP00000397805.1	H7C105

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 3836 AN: 41374 Hom.: 68 Cov.: 23

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0459

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.0263

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0403 AC: 18247 AN: 452488 Hom.: 113 Cov.: 6 AF XY: 0.0394 AC XY: 8993 AN XY: 228008

African (AFR) AF: 0.0134 AC: 149 AN: 11150

American (AMR) AF: 0.0201 AC: 188 AN: 9344

Ashkenazi Jewish (ASJ) AF: 0.0413 AC: 424 AN: 10266

East Asian (EAS) AF: 0.0176 AC: 387 AN: 22046

South Asian (SAS) AF: 0.0200 AC: 517 AN: 25806

European-Finnish (FIN) AF: 0.0235 AC: 654 AN: 27776

Middle Eastern (MID) AF: 0.0234 AC: 40 AN: 1708

European-Non Finnish (NFE) AF: 0.0468 AC: 15081 AN: 322092

Other (OTH) AF: 0.0362 AC: 807 AN: 22300

GnomAD4 genome AF: 0.0927 AC: 3837 AN: 41402 Hom.: 68 Cov.: 23 AF XY: 0.0878 AC XY: 1720 AN XY: 19580

African (AFR) AF: 0.0465 AC: 474 AN: 10188

American (AMR) AF: 0.122 AC: 344 AN: 2814

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 124 AN: 1118

East Asian (EAS) AF: 0.0459 AC: 89 AN: 1940

South Asian (SAS) AF: 0.0392 AC: 50 AN: 1274

European-Finnish (FIN) AF: 0.0478 AC: 107 AN: 2240

Middle Eastern (MID) AF: 0.0294 AC: 1 AN: 34

European-Non Finnish (NFE) AF: 0.121 AC: 2549 AN: 20986

Other (OTH) AF: 0.103 AC: 55 AN: 536

Alfa AF: 0.00698 Hom.: 2

Bravo AF: 0.0266

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.031
Mutation Taster		=100/0	polymorphism

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: rs377485634; hg19: chr22-28146769;