Variant chr11-108317312-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000051.4(ATM):c.6199-61C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 1,536,150 control chromosomes in the GnomAD database, including 1,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 107 hom., cov: 28)

Exomes 𝑓: 0.038 ( 1094 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.214

Variant links:

Genes affected

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 links:

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:):

ATM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-108317312-C-G is Benign according to our data. Variant chr11-108317312-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1228645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108317312-C-G is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4 linkuse as main transcript	c.6199-61C>G		intron_variant		ENST00000675843.1	NP_000042.3	Q13315A0A024R3C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1 linkuse as main transcript	c.6199-61C>G		intron_variant			NM_000051.4	ENSP00000501606.1		Q13315

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4518

AN:

151738

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00665

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0235

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0382

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0455

Gnomad OTH

AF:

0.0302

GnomAD4 exome

AF:

0.0379

AC:

52526

AN:

1384294

Hom.:

1094

AF XY:

0.0380

AC XY:

26247

AN XY:

691042

show subpopulations

Gnomad4 AFR exome

AF:

0.00619

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0465

Gnomad4 EAS exome

AF:

0.000131

Gnomad4 SAS exome

AF:

0.0299

Gnomad4 FIN exome

AF:

0.0397

Gnomad4 NFE exome

AF:

0.0411

Gnomad4 OTH exome

AF:

0.0378

GnomAD4 genome

AF:

0.0297

AC:

4517

AN:

151856

Hom.:

107

Cov.:

AF XY:

0.0298

AC XY:

2213

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.00663

Gnomad4 AMR

AF:

0.0234

Gnomad4 ASJ

AF:

0.0447

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.0287

Gnomad4 FIN

AF:

0.0382

Gnomad4 NFE

AF:

0.0455

Gnomad4 OTH

AF:

0.0304

Alfa

AF:

0.0371

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Hereditary breast ovarian cancer syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.4

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over