11-94466544-C-T

Position:

• chr11-94466544-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MRE11	NM_005591.4	c.1098+1269G>A		intron_variant		ENST00000323929.8	NP_005582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRE11	ENST00000323929.8	c.1098+1269G>A		intron_variant		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

GnomAD3 exomes AF: 0.0250 AC: 5976 AN: 238692 Hom.: 212 AF XY: 0.0252 AC XY: 3281 AN XY: 130426

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 SAS exome AF: 0.0453

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

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0149

Gnomad4 ASJ exome AF: 0.0338

Gnomad4 EAS exome AF: 0.000155

Gnomad4 SAS exome AF: 0.0461

Gnomad4 FIN exome AF: 0.00106

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.0276

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

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0253 Hom.: 83

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

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

LitVar

Other links and lift over

dbSNP: rs11020790; hg19: chr11-94199710;