chr11-94488198-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005591.4(MRE11):​c.154-2114T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,040 control chromosomes in the GnomAD database, including 21,253 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 21253 hom., cov: 32)

Consequence

MRE11
NM_005591.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

3 publications found
Variant links:
Genes affected
MRE11 (HGNC:7230): (MRE11 homolog, double strand break repair nuclease) This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
MRE11 Gene-Disease associations (from GenCC):
  • ataxia-telangiectasia-like disorder 1
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
  • breast cancer
    Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
  • familial ovarian cancer
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
  • hereditary breast carcinoma
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
  • prostate cancer
    Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRE11NM_005591.4 linkc.154-2114T>C intron_variant Intron 3 of 19 ENST00000323929.8 NP_005582.1 P49959-1A0A024R395

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRE11ENST00000323929.8 linkc.154-2114T>C intron_variant Intron 3 of 19 1 NM_005591.4 ENSP00000325863.4 P49959-1

Frequencies

GnomAD3 genomes
AF:
0.520
AC:
78975
AN:
151922
Hom.:
21231
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.660
Gnomad AMI
AF:
0.227
Gnomad AMR
AF:
0.540
Gnomad ASJ
AF:
0.448
Gnomad EAS
AF:
0.492
Gnomad SAS
AF:
0.602
Gnomad FIN
AF:
0.466
Gnomad MID
AF:
0.598
Gnomad NFE
AF:
0.442
Gnomad OTH
AF:
0.522
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.520
AC:
79046
AN:
152040
Hom.:
21253
Cov.:
32
AF XY:
0.524
AC XY:
38957
AN XY:
74342
show subpopulations
African (AFR)
AF:
0.660
AC:
27365
AN:
41466
American (AMR)
AF:
0.540
AC:
8247
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.448
AC:
1557
AN:
3472
East Asian (EAS)
AF:
0.491
AC:
2533
AN:
5160
South Asian (SAS)
AF:
0.604
AC:
2914
AN:
4828
European-Finnish (FIN)
AF:
0.466
AC:
4925
AN:
10564
Middle Eastern (MID)
AF:
0.599
AC:
176
AN:
294
European-Non Finnish (NFE)
AF:
0.442
AC:
30035
AN:
67954
Other (OTH)
AF:
0.515
AC:
1087
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1924
3848
5772
7696
9620
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
694
1388
2082
2776
3470
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.483
Hom.:
2388
Bravo
AF:
0.528
Asia WGS
AF:
0.531
AC:
1844
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.38
DANN
Benign
0.69
PhyloP100
-1.9
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

Publications

Other links and lift over

dbSNP: rs2508784; hg19: chr11-94221364; API