chr11-64804931-C-G

Variant names:

• chr11-64804931-C-G
• rs654440
• NM_001370259.2:c.1350+103G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370259.2(MEN1):​c.1350+103G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,598,060 control chromosomes in the GnomAD database, including 159,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (10209 hom., cov: 34)
  • Exomes 𝑓: 0.44 (148805 hom.)
• Consequence: MEN1 NM_001370259.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.61
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-64804931-C-G is Benign according to our data. Variant chr11-64804931-C-G is described in ClinVar as Benign. ClinVar VariationId is 1245707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2	c.1350+103G>C		intron_variant	Intron 9 of 9	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7	c.1350+103G>C		intron_variant	Intron 9 of 9	5	NM_001370259.2	ENSP00000394933.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48693 AN: 152078 Hom.: 10216 Cov.: 34

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.00960

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.437 AC: 632254 AN: 1445864 Hom.: 148805 Cov.: 41 AF XY: 0.434 AC XY: 312579 AN XY: 719668

African (AFR) AF: 0.0741 AC: 2480 AN: 33454

American (AMR) AF: 0.217 AC: 9707 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 13155 AN: 26126

East Asian (EAS) AF: 0.00315 AC: 125 AN: 39686

South Asian (SAS) AF: 0.279 AC: 24027 AN: 86012

European-Finnish (FIN) AF: 0.423 AC: 16598 AN: 39278

Middle Eastern (MID) AF: 0.402 AC: 2206 AN: 5488

European-Non Finnish (NFE) AF: 0.485 AC: 539319 AN: 1110894

Other (OTH) AF: 0.409 AC: 24637 AN: 60216

GnomAD4 genome AF: 0.320 AC: 48680 AN: 152196 Hom.: 10209 Cov.: 34 AF XY: 0.314 AC XY: 23332 AN XY: 74388

African (AFR) AF: 0.0867 AC: 3601 AN: 41554

American (AMR) AF: 0.281 AC: 4291 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1699 AN: 3468

East Asian (EAS) AF: 0.00963 AC: 50 AN: 5194

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4818

European-Finnish (FIN) AF: 0.400 AC: 4239 AN: 10590

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32103 AN: 67958

Other (OTH) AF: 0.343 AC: 726 AN: 2114

Alfa AF: 0.394 Hom.: 1679

Bravo AF: 0.305

Asia WGS AF: 0.122 AC: 428 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.65
PhyloP100		1.6
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: rs654440; hg19: chr11-64572403;