rs1805360

Variant names:

• chr11-94493863-C-T
• rs1805360
• ENST00000323977.7:c.-285G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-94493863-C-T
• chr11-94493863-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000323977.7(MRE11):​c.-285G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 152,346 control chromosomes in the GnomAD database, including 271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (271 hom., cov: 32)
  • Exomes 𝑓: 0.018 (0 hom.)
• Consequence: MRE11 ENST00000323977.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.189
• Publications: 6 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]

ANKRD49 (HGNC:25970): (ankyrin repeat domain 49) Involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-94493863-C-T is Benign according to our data. Variant chr11-94493863-C-T is described in ClinVar as Benign. ClinVar VariationId is 306499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000323977.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRE11	NM_005591.4	MANE Select	c.-178G>A		upstream_gene	N/A	NP_005582.1	P49959-1
	ANKRD49	NM_017704.3	MANE Select	c.-263C>T		upstream_gene	N/A	NP_060174.2
	MRE11	NM_001440460.1		c.-178G>A		upstream_gene	N/A	NP_001427389.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRE11	ENST00000323977.7	TSL:1	c.-285G>A		5_prime_UTR	Exon 1 of 19	ENSP00000326094.3	P49959-2
	MRE11	ENST00000856310.1		c.-285G>A		5_prime_UTR	Exon 1 of 20	ENSP00000526369.1
	MRE11	ENST00000856316.1		c.-178G>A		5_prime_UTR	Exon 1 of 20	ENSP00000526375.1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5834 AN: 152172 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.0179 AC: 1 AN: 56 Hom.: 0 Cov.: 0 AF XY: 0.0217 AC XY: 1 AN XY: 46

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0383 AC: 5836 AN: 152290 Hom.: 271 Cov.: 32 AF XY: 0.0377 AC XY: 2805 AN XY: 74478

African (AFR) AF: 0.107 AC: 4445 AN: 41556

American (AMR) AF: 0.0190 AC: 291 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 88 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.0366 AC: 177 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 728 AN: 68022

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0240 Hom.: 178

Bravo AF: 0.0428

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Ataxia-telangiectasia-like disorder 1 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.6
DANN	Benign	0.89
PhyloP100		-0.19
PromoterAI		-0.074	Neutral
Mutation Taster		=300/0	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: rs1805360; hg19: chr11-94227029; COSMIC: COSV57060755;