rs664143

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000615746.4(C11orf65):c.*1177T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,389,134 control chromosomes in the GnomAD database, including 241,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29318 hom., cov: 32)

Exomes 𝑓: 0.58 ( 212111 hom. )

Consequence

C11orf65
ENST00000615746.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.696

Publications

76 publications found

Variant links:

Genes affected

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

C11orf65 links:

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

ATM Gene-Disease associations (from GenCC):

ATM-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
ataxia telangiectasia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Laboratory for Molecular Medicine
prostate cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
gastric carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 11-108354934-A-G is Benign according to our data. Variant chr11-108354934-A-G is described in ClinVar as Benign. ClinVar VariationId is 1169174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	NM_000051.4	MANE Select	c.8850+60A>G	intron	N/A	NP_000042.3
ATM	NM_001351834.2		c.8850+60A>G	intron	N/A	NP_001338763.1	Q13315
C11orf65	NM_001330368.2		c.640+30986T>C	intron	N/A	NP_001317297.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C11orf65	ENST00000615746.4	TSL:1	c.*1177T>C	3_prime_UTR	Exon 11 of 13	ENSP00000483537.1	Q8NCR3-1
ATM	ENST00000675843.1	MANE Select	c.8850+60A>G	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.8850+60A>G	intron	N/A	ENSP00000388058.2	Q13315

Frequencies

GnomAD3 genomes

AF:

0.618

AC:

93911

AN:

151958

Hom.:

29289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.676

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.662

Gnomad ASJ

AF:

0.670

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.628

GnomAD4 exome

AF:

0.583

AC:

721636

AN:

1237056

Hom.:

212111

Cov.:

AF XY:

0.587

AC XY:

367518

AN XY:

626590

show subpopulations

African (AFR)

AF:

0.678

AC:

19629

AN:

28954

American (AMR)

AF:

0.658

AC:

29080

AN:

44170

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

15965

AN:

24754

East Asian (EAS)

AF:

0.466

AC:

17977

AN:

38588

South Asian (SAS)

AF:

0.648

AC:

52901

AN:

81588

European-Finnish (FIN)

AF:

0.626

AC:

31035

AN:

49552

Middle Eastern (MID)

AF:

0.752

AC:

4044

AN:

5380

European-Non Finnish (NFE)

AF:

0.570

AC:

519428

AN:

911030

Other (OTH)

AF:

0.595

AC:

31577

AN:

53040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

15234

30468

45703

60937

76171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13266

26532

39798

53064

66330

<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:

0.618

AC:

93986

AN:

152078

Hom.:

29318

Cov.:

AF XY:

0.622

AC XY:

46256

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.676

AC:

28062

AN:

41484

American (AMR)

AF:

0.661

AC:

10096

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

2324

AN:

3470

East Asian (EAS)

AF:

0.445

AC:

2306

AN:

5178

South Asian (SAS)

AF:

0.652

AC:

3145

AN:

4820

European-Finnish (FIN)

AF:

0.631

AC:

6669

AN:

10566

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.577

AC:

39249

AN:

67980

Other (OTH)

AF:

0.628

AC:

1327

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1836

3672

5507

7343

9179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.593

Hom.:

68623

Bravo

AF:

0.620

Asia WGS

AF:

0.599

AC:

2084

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Ataxia-telangiectasia syndrome (1)

Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.53

(source)

DANN

Benign

0.37

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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