rs2509943

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.25

Publications

18 publications found

Variant links:

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]

ANKRD49 links:

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]

MRE11 Gene-Disease associations (from GenCC):

ataxia-telangiectasia-like disorder 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
prostate cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

MRE11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017704.3. 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
	ANKRD49	NM_017704.3	MANE Select	c.279C>G	p.Leu93Leu	synonymous	Exon 3 of 3	NP_060174.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD49	ENST00000544612.6	TSL:1 MANE Select	c.279C>G	p.Leu93Leu	synonymous	Exon 3 of 3	ENSP00000440396.1	Q8WVL7
ANKRD49	ENST00000302755.4	TSL:1	c.279C>G	p.Leu93Leu	synonymous	Exon 2 of 2	ENSP00000303518.3	Q8WVL7
ANKRD49	ENST00000544253.1	TSL:1	c.*1020C>G		3_prime_UTR	Exon 2 of 2	ENSP00000446433.1	F6R851

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86744

AN:

151774

Hom.:

25026

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.533

AC:

132508

AN:

248708

AF XY:

0.530

show subpopulations

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 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.:

AF XY:

0.553

AC XY:

400514

AN XY:

724704

show subpopulations

African (AFR)

AF:

0.626

AC:

20894

AN:

33356

American (AMR)

AF:

0.467

AC:

20723

AN:

44408

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

14615

AN:

25950

East Asian (EAS)

AF:

0.484

AC:

19194

AN:

39618

South Asian (SAS)

AF:

0.431

AC:

37061

AN:

86024

European-Finnish (FIN)

AF:

0.542

AC:

28582

AN:

52730

Middle Eastern (MID)

AF:

0.518

AC:

2953

AN:

5704

European-Non Finnish (NFE)

AF:

0.572

AC:

634213

AN:

1109598

Other (OTH)

AF:

0.558

AC:

33573

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

17208

34416

51625

68833

86041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17626

35252

52878

70504

88130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.572

AC:

86817

AN:

151892

Hom.:

25048

Cov.:

AF XY:

0.565

AC XY:

41962

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.630

AC:

26076

AN:

41412

American (AMR)

AF:

0.498

AC:

7586

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.586

AC:

2032

AN:

3468

East Asian (EAS)

AF:

0.521

AC:

2689

AN:

5164

South Asian (SAS)

AF:

0.434

AC:

2089

AN:

4814

European-Finnish (FIN)

AF:

0.535

AC:

5646

AN:

10548

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38683

AN:

67932

Other (OTH)

AF:

0.559

AC:

1176

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1883

3766

5650

7533

9416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.534

Hom.:

5607

Bravo

AF:

0.575

Asia WGS

AF:

0.500

AC:

1739

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.44

(source)

DANN

Benign

0.63

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over