chr11-94466544-C-T

Variant names:

• chr11-94466544-C-T
• rs11020790
• NM_005591.4:c.1098+1269G>A

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+1269G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 523,486 control chromosomes in the GnomAD database, including 719 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 0.049 (447 hom., cov: 32)
  • Exomes 𝑓: 0.022 (272 hom.)
• Consequence: MRE11 NM_005591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRE11	NM_005591.4	c.1098+1269G>A		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+1269G>A		intron_variant	Intron 10 of 19	1	NM_005591.4	ENSP00000325863.4

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7441 AN: 152074 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0512

GnomAD2 exomes AF: 0.0250 AC: 5976 AN: 238692 AF XY: 0.0252

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.0149

Gnomad ASJ exome AF: 0.0355

Gnomad EAS exome AF: 0.000169

Gnomad FIN exome AF: 0.00108

Gnomad NFE exome AF: 0.0130

Gnomad OTH exome AF: 0.0247

GnomAD4 exome AF: 0.0224 AC: 8313 AN: 371294 Hom.: 272 Cov.: 0 AF XY: 0.0242 AC XY: 5109 AN XY: 211500

African (AFR) AF: 0.140 AC: 1446 AN: 10348

American (AMR) AF: 0.0149 AC: 538 AN: 36152

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 394 AN: 11654

East Asian (EAS) AF: 0.000155 AC: 2 AN: 12872

South Asian (SAS) AF: 0.0461 AC: 3064 AN: 66504

European-Finnish (FIN) AF: 0.00106 AC: 28 AN: 26450

Middle Eastern (MID) AF: 0.0724 AC: 205 AN: 2832

European-Non Finnish (NFE) AF: 0.0116 AC: 2183 AN: 188064

Other (OTH) AF: 0.0276 AC: 453 AN: 16418

GnomAD4 genome AF: 0.0489 AC: 7445 AN: 152192 Hom.: 447 Cov.: 32 AF XY: 0.0476 AC XY: 3540 AN XY: 74428

African (AFR) AF: 0.140 AC: 5826 AN: 41498

American (AMR) AF: 0.0230 AC: 352 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0125 AC: 847 AN: 68020

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0274 Hom.: 100

Bravo AF: 0.0545

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.3
DANN	Benign	0.76
PhyloP100		-1.2
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: rs11020790; hg19: chr11-94199710;