11-64804025-CGAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001370259.2(MEN1):c.*306_*308del 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MEN1	NM_001370259.2	c.*306_*308del		3_prime_UTR_variant	10/10	ENST00000450708.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEN1	ENST00000450708.7	c.*306_*308del		3_prime_UTR_variant	10/10	5	NM_001370259.2	P3

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

Gnomad4 AFR exome AF: 0.00339

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.00634

Gnomad4 FIN exome AF: 0.00596

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.0227

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

Gnomad4 AFR AF: 0.00383

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.00892

Gnomad4 FIN AF: 0.00726

Gnomad4 NFE AF: 0.00166

Gnomad4 OTH AF: 0.0308

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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hyperparathyroidism Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs143341556; hg19: chr11-64571497;