11-64804025-CGAG-C

Variant names:

• chr11-64804025-CGAG-C
• rs143341556
• NM_001370259.2:c.*306_*308delCTC

Variant summary

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

The NM_001370259.2(MEN1):​c.*306_*308delCTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 469,412 control chromosomes in the GnomAD database, including 1,525 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (462 hom., cov: 32)
  • Exomes 𝑓: 0.029 (1063 hom.)
• Consequence: MEN1 NM_001370259.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.108
• Publications: 0 publications found

Genes affected

MEN1 (HGNC:7010): (menin 1) This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]

MEN1 Gene-Disease associations (from GenCC):

• multiple endocrine neoplasia type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics
• familial isolated hyperparathyroidism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pituitary gigantism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP6: Variant 11-64804025-CGAG-C is Benign according to our data. Variant chr11-64804025-CGAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 305306.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2	c.*306_*308delCTC		3_prime_UTR_variant	Exon 10 of 10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.*306_*308delCTC		3_prime_UTR_variant	Exon 10 of 10	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4238 AN: 152004 Hom.: 461 Cov.: 32

Gnomad AFR AF: 0.00384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.00726

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0294 AC: 9338 AN: 317290 Hom.: 1063 AF XY: 0.0268 AC XY: 4435 AN XY: 165620

African (AFR) AF: 0.00339 AC: 35 AN: 10320

American (AMR) AF: 0.216 AC: 3036 AN: 14064

Ashkenazi Jewish (ASJ) AF: 0.00139 AC: 15 AN: 10828

East Asian (EAS) AF: 0.247 AC: 5256 AN: 21250

South Asian (SAS) AF: 0.00634 AC: 264 AN: 41622

European-Finnish (FIN) AF: 0.00596 AC: 72 AN: 12088

Middle Eastern (MID) AF: 0.00220 AC: 3 AN: 1364

European-Non Finnish (NFE) AF: 0.00125 AC: 234 AN: 187106

Other (OTH) AF: 0.0227 AC: 423 AN: 18648

GnomAD4 genome AF: 0.0279 AC: 4248 AN: 152122 Hom.: 462 Cov.: 32 AF XY: 0.0325 AC XY: 2413 AN XY: 74356

African (AFR) AF: 0.00383 AC: 159 AN: 41510

American (AMR) AF: 0.174 AC: 2658 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1131 AN: 5162

South Asian (SAS) AF: 0.00892 AC: 43 AN: 4818

European-Finnish (FIN) AF: 0.00726 AC: 77 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00166 AC: 113 AN: 67998

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0129 Hom.: 18

Bravo AF: 0.0427

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Multiple endocrine neoplasia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyperparathyroidism Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
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: rs143341556; hg19: chr11-64571497;