11-108281855-C-T

Variant names:

• chr11-108281855-C-T
• rs1003623
• NM_000051.4:c.3576+687C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000051.4(ATM):​c.3576+687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,984 control chromosomes in the GnomAD database, including 21,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.53 (21787 hom., cov: 33)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.388

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BP6: Variant 11-108281855-C-T is Benign according to our data. Variant chr11-108281855-C-T is described in ClinVar as [Benign]. Clinvar id is 489536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.3576+687C>T		intron_variant	Intron 24 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.3576+687C>T		intron_variant	Intron 24 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79817 AN: 151866 Hom.: 21776 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.525 AC: 79852 AN: 151984 Hom.: 21787 Cov.: 33 AF XY: 0.534 AC XY: 39661 AN XY: 74284

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.560

Alfa AF: 0.336 Hom.: 725

Bravo AF: 0.514

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary cancer-predisposing syndrome Benign:1

Nov 26, 2014

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.0
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs1003623; hg19: chr11-108152582;