Variant chr11-108223106-G-A 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.-111G>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 0.497 in 180,500 control chromosomes in the GnomAD database, including 24,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20089 hom., cov: 32)

Exomes 𝑓: 0.52 ( 4049 hom. )

Consequence

ATM
NM_000051.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.618

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:

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=-0.56).

BP6

Variant 11-108223106-G-A is Benign according to our data. Variant chr11-108223106-G-A is described in ClinVar as [Benign]. Clinvar id is 302240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108223106-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.6 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.-111G>A		5_prime_UTR_variant	1/63	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1 linkuse as main transcript	c.-111G>A		5_prime_UTR_variant	1/63		NM_000051.4	ENSP00000501606	P1

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74964

AN:

151940

Hom.:

20079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.732

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.539

GnomAD4 exome

AF:

0.515

AC:

14650

AN:

28442

Hom.:

4049

Cov.:

AF XY:

0.523

AC XY:

8065

AN XY:

15418

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.615

Gnomad4 ASJ exome

AF:

0.544

Gnomad4 EAS exome

AF:

0.384

Gnomad4 SAS exome

AF:

0.555

Gnomad4 FIN exome

AF:

0.507

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.512

GnomAD4 genome

AF:

0.493

AC:

74993

AN:

152058

Hom.:

20089

Cov.:

AF XY:

0.502

AC XY:

37304

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.610

Gnomad4 ASJ

AF:

0.642

Gnomad4 EAS

AF:

0.423

Gnomad4 SAS

AF:

0.601

Gnomad4 FIN

AF:

0.630

Gnomad4 NFE

AF:

0.568

Gnomad4 OTH

AF:

0.540

Alfa

AF:

0.520

Hom.:

2904

Bravo

AF:

0.480

Asia WGS

AF:

0.534

AC:

1854

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ataxia-telangiectasia syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 20816691, 22529920, 22960875, 20004998, 21108427, 23993922, 21937043) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.8

DANN

Benign

0.96

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