chr11-64805130-G-A

Variant names:

• chr11-64805130-G-A
• rs2071313
• NM_001370259.2:c.1254C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001370259.2(MEN1):​c.1254C>T​(p.Asp418Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,613,902 control chromosomes in the GnomAD database, including 132,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9444 hom., cov: 33)
  • Exomes 𝑓: 0.40 (122584 hom.)
• Consequence: MEN1 NM_001370259.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:18
• Conservation: PhyloP100: 0.00600
• Publications: 47 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen, 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 11-64805130-G-A is Benign according to our data. Variant chr11-64805130-G-A is described in ClinVar as Benign. ClinVar VariationId is 96249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.006 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370259.2. 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
	MEN1	NM_001370259.2	MANE Select	c.1254C>T	p.Asp418Asp	synonymous	Exon 9 of 10	NP_001357188.2	O00255-2
	MEN1	NM_001407150.1		c.1395C>T	p.Asp465Asp	synonymous	Exon 10 of 11	NP_001394079.1
	MEN1	NM_001370251.2		c.1380C>T	p.Asp460Asp	synonymous	Exon 10 of 11	NP_001357180.2	A0A5F9ZHS3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEN1	ENST00000450708.7	TSL:5 MANE Select	c.1254C>T	p.Asp418Asp	synonymous	Exon 9 of 10	ENSP00000394933.3	O00255-2
	MEN1	ENST00000312049.11	TSL:1	c.1254C>T	p.Asp418Asp	synonymous	Exon 9 of 10	ENSP00000308975.6	O00255-2
	MEN1	ENST00000424912.2	TSL:1	c.1254C>T	p.Asp418Asp	synonymous	Exon 10 of 11	ENSP00000388016.2	O00255-2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48417 AN: 152064 Hom.: 9443 Cov.: 33

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.392 AC: 98289 AN: 250996 AF XY: 0.404

Gnomad AFR exome AF: 0.0819

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.346

Gnomad EAS exome AF: 0.384

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.421

Gnomad OTH exome AF: 0.396

GnomAD4 exome AF: 0.405 AC: 591624 AN: 1461718 Hom.: 122584 Cov.: 56 AF XY: 0.409 AC XY: 297212 AN XY: 727164

African (AFR) AF: 0.0756 AC: 2530 AN: 33478

American (AMR) AF: 0.334 AC: 14948 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 8901 AN: 26132

East Asian (EAS) AF: 0.381 AC: 15145 AN: 39700

South Asian (SAS) AF: 0.481 AC: 41522 AN: 86254

European-Finnish (FIN) AF: 0.436 AC: 23263 AN: 53376

Middle Eastern (MID) AF: 0.440 AC: 2522 AN: 5738

European-Non Finnish (NFE) AF: 0.413 AC: 459266 AN: 1111936

Other (OTH) AF: 0.390 AC: 23527 AN: 60396

GnomAD4 genome AF: 0.318 AC: 48421 AN: 152184 Hom.: 9444 Cov.: 33 AF XY: 0.322 AC XY: 23940 AN XY: 74382

African (AFR) AF: 0.0893 AC: 3709 AN: 41546

American (AMR) AF: 0.325 AC: 4968 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1223 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1956 AN: 5162

South Asian (SAS) AF: 0.491 AC: 2366 AN: 4822

European-Finnish (FIN) AF: 0.452 AC: 4793 AN: 10594

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28305 AN: 67980

Other (OTH) AF: 0.347 AC: 731 AN: 2108

Alfa AF: 0.336 Hom.: 9264

Bravo AF: 0.294

Asia WGS AF: 0.434 AC: 1508 AN: 3478

EpiCase AF: 0.414

EpiControl AF: 0.411

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	5	Multiple endocrine neoplasia, type 1 (5)
-	-	3	not provided (3)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	1	Hyperparathyroidism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.1
DANN	Benign	0.89
PhyloP100		0.0060
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=98/2	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: rs2071313; hg19: chr11-64572602; COSMIC: COSV53640840; COSMIC: COSV53640840;