rs13447640

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_005591.4(MRE11):c.1098+1258C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 517,188 control chromosomes in the GnomAD database, including 664 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 0.046 ( 411 hom., cov: 32)

Exomes 𝑓: 0.022 ( 253 hom. )

Consequence

MRE11
NM_005591.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.74

Publications

12 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 links:

MIR548L (HGNC:35292): (microRNA 548l) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR548L links:

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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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005591.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRE11	NM_005591.4	MANE Select	c.1098+1258C>T	intron	N/A	NP_005582.1	P49959-1
MRE11	NM_001440460.1		c.1098+1258C>T	intron	N/A	NP_001427389.1
MRE11	NM_001440461.1		c.1098+1258C>T	intron	N/A	NP_001427390.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRE11	ENST00000323929.8	TSL:1 MANE Select	c.1098+1258C>T	intron	N/A	ENSP00000325863.4	P49959-1
MRE11	ENST00000323977.7	TSL:1	c.1098+1258C>T	intron	N/A	ENSP00000326094.3	P49959-2
MRE11	ENST00000936196.1		c.1098+1258C>T	intron	N/A	ENSP00000606255.1

Frequencies

GnomAD3 genomes

AF:

0.0464

AC:

7057

AN:

152058

Hom.:

409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0503

GnomAD2 exomes

AF:

0.0241

AC:

5626

AN:

233402

AF XY:

0.0244

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.000790

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0241

GnomAD4 exome

AF:

0.0215

AC:

7866

AN:

365012

Hom.:

253

Cov.:

AF XY:

0.0234

AC XY:

4867

AN XY:

207642

show subpopulations

African (AFR)

AF:

0.134

AC:

1368

AN:

10226

American (AMR)

AF:

0.0143

AC:

515

AN:

35898

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

391

AN:

11614

East Asian (EAS)

AF:

0.000158

AC:

AN:

12674

South Asian (SAS)

AF:

0.0458

AC:

3032

AN:

66234

European-Finnish (FIN)

AF:

0.000737

AC:

AN:

24408

Middle Eastern (MID)

AF:

0.0719

AC:

203

AN:

2824

European-Non Finnish (NFE)

AF:

0.0103

AC:

1899

AN:

184920

Other (OTH)

AF:

0.0270

AC:

438

AN:

16214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

288

577

865

1154

1442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0464

AC:

7060

AN:

152176

Hom.:

411

Cov.:

AF XY:

0.0454

AC XY:

3378

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.134

AC:

5571

AN:

41492

American (AMR)

AF:

0.0220

AC:

337

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

114

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0109

AC:

738

AN:

68004

Other (OTH)

AF:

0.0498

AC:

105

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

318

636

955

1273

1591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0184

Hom.:

Bravo

AF:

0.0519

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.5

(source)

DANN

Benign

0.78

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over