rs13447640

Variant names:

• chr11-94466555-G-A
• rs13447640
• NM_005591.4:c.1098+1258C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-94466555-G-A
• chr11-94466555-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 12 publications found

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]

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4	c.1098+1258C>T		intron_variant	Intron 10 of 19	ENST00000323929.8	NP_005582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8	c.1098+1258C>T		intron_variant	Intron 10 of 19	1	NM_005591.4	ENSP00000325863.4

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7057 AN: 152058 Hom.: 409 Cov.: 32

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

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.: 0 AF XY: 0.0234 AC XY: 4867 AN XY: 207642

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: 2 AN: 12674

South Asian (SAS) AF: 0.0458 AC: 3032 AN: 66234

European-Finnish (FIN) AF: 0.000737 AC: 18 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

GnomAD4 genome AF: 0.0464 AC: 7060 AN: 152176 Hom.: 411 Cov.: 32 AF XY: 0.0454 AC XY: 3378 AN XY: 74402

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: 2 AN: 5178

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 738 AN: 68004

Other (OTH) AF: 0.0498 AC: 105 AN: 2108

Alfa AF: 0.0184 Hom.: 22

Bravo AF: 0.0519

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.78
PhyloP100		-2.7
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: rs13447640; hg19: chr11-94199721;