11-94498091-C-G

Variant names:

• chr11-94498091-C-G
• rs2509943
• NM_017704.3:c.279C>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017704.3(ANKRD49):​c.279C>G​(p.Leu93Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,609,474 control chromosomes in the GnomAD database, including 252,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25048 hom., cov: 31)
  • Exomes 𝑓: 0.56 (227892 hom.)
• Consequence: ANKRD49 NM_017704.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-94498091-C-G is Benign according to our data. Variant chr11-94498091-C-G is described in ClinVar as [Benign]. Clinvar id is 403103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD49	NM_017704.3	c.279C>G	p.Leu93Leu	synonymous_variant	Exon 3 of 3	ENST00000544612.6	NP_060174.2
ANKRD49	XM_017017941.2	c.279C>G	p.Leu93Leu	synonymous_variant	Exon 3 of 3		XP_016873430.1
MRE11	XM_011542837.3	c.-105-5185G>C		intron_variant	Intron 1 of 19		XP_011541139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD49	ENST00000544612.6	c.279C>G	p.Leu93Leu	synonymous_variant	Exon 3 of 3	1	NM_017704.3	ENSP00000440396.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86744 AN: 151774 Hom.: 25026 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.553

GnomAD3 exomes AF: 0.533 AC: 132508 AN: 248708 Hom.: 35769 AF XY: 0.530 AC XY: 71214 AN XY: 134440

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.460

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.520

Gnomad SAS exome AF: 0.433

Gnomad FIN exome AF: 0.540

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.540

GnomAD4 exome AF: 0.557 AC: 811808 AN: 1457582 Hom.: 227892 Cov.: 39 AF XY: 0.553 AC XY: 400514 AN XY: 724704

Gnomad4 AFR exome AF: 0.626

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.542

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.572 AC: 86817 AN: 151892 Hom.: 25048 Cov.: 31 AF XY: 0.565 AC XY: 41962 AN XY: 74222

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.559

Alfa AF: 0.534 Hom.: 5607

Bravo AF: 0.575

Asia WGS AF: 0.500 AC: 1739 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.44
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2509943; hg19: chr11-94231257; COSMIC: COSV57060945; COSMIC: COSV57060945;